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Lung Circulation

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ABSTRACT

The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed. © 2016 American Physiological Society. Compr Physiol 6:897‐943, 2016.

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Figure 1. Figure 1. Timeline of vascular development. Adapted, with permission, from Hislop and Pierce ().
Figure 2. Figure 2. Arteriogram of a human lung obtained postmortem from a fetus (39 weeks gestation) showing distal vascularization. The arteries were injected with barium sulphate (mag × 0.75). Reprinted, with permission, from ().
Figure 3. Figure 3. Graph illustrating the relationship between PVR and volume. Adapted, with permission, from ().
Figure 4. Figure 4. Original three‐zone model proposed by West et al., () to illustrate the regional heterogeneity in blood flow. Within each of the three zones, the behavior of the blood vessels is different, based on the relative magnitudes of pulmonary arterial, alveolar and venous pressures (Pa, PA, and Pv, respectively). In zone 1, PA is greater than Pa, occluding collapsible vessels and preventing flow. In zone 2, Pa is greater than PA, which exceeds Pv, such that blood flow is dictated by the Pa‐PA pressure gradient. In zone 3, both Pa and Pv exceed PA, and vessels are held open, allowing blood flow based on the Pa‐Pv pressure gradient. Reproduced, with permission, from West et al. ().
Figure 5. Figure 5. Effect of PEEP and no, or zero, end expiratory pressure on VR and CO. (A) Effect of PEEP on CO and VR if PEEP has no effects on venous return flow limitation. Points A and B represent effects of PEEP without changes in mean systemic pressure (Pms). Point C represents effect of PEEP with Pms compensation. (B) Effect of PEEP on CO and venous return if increased VR flow limitation (FL2) occurs with higher PEEP. Reprinted, with permission, from Luecke and Pelosi ().
Figure 6. Figure 6. Proposed mechanisms by which hypoxia caused pulmonary vasoconstriction. Reproduced, with permission, from Sylvester et al. ().
Figure 7. Figure 7. The lung‐on‐a‐chip microdevice. (A) Compartmentalized channels form an alveolar‐capillary barrier on a thin, porous, flexible membrane. Physiological breathing movements are mimicked by applying a vacuum to the side chambers, causing mechanical stretching of the membrane that forms the alveolar‐capillary barrier. (B) Cartoon illustrating the mechanical effects of inspiration in the living lung, where contraction of the diaphragm reduced pleural pressure (Pip), resulting in distension of alveoli and physical stretching of the alveolar‐capillary interface. (C) The three‐layer system forming parallel microchannels with a porous membrane. Scale bar, 200 μm. (D) After the three layers are bonded together, the membrane layers in the side channels are removed, producing two side chambers to which vacuum is applied to cause mechanical stretching. Scale bar, 200 μm. (E) Actual images of a lung‐on‐a‐chip device. Reproduced, with permission, from ().
Figure 8. Figure 8. Illustration of putative mechanisms involved in the pathogenesis of pulmonary hypertension. Abbreviations: 5‐HT, 5‐hydroxytryptamin; K‐ and Ca‐channels, potassium and calcium channels; AEC, alveolar epithelial cells; BMP, bone morphogenetic protein; cGMP, cyclic guanosine monophosphate; ECM, extracellular matrix; EGF, epidermal growth factor; EPC, endothelial progenitor cells; HIF, hypoxia inducible factor; MMPs, matrix metalloproteinases; NADPH, nicotinamide adenine dinucleotide phosphate; NO, nitric oxide; PDE, phosphodiesterase; PDGF, platelet‐derived growth factor; PGI2, prostaglandin I2; Rho‐Ki, Rho kinases; ROS, reactive oxygen species; sGC, soluble guanylate cyclase; TGF, transforming growth factor‐β; TK, tyrosine kinase; TKi, tyrosine kinase inhibitor; TRPC, transient receptor potential cation channels; VEGF, vascular endothelial growth factor. Reproduced, with permission, from Schermuly et al. ().
Figure 9. Figure 9. Drawing by Fredrick Ruysch detailing the bronchial circulation. Reproduced, with permission, from Mitzner ().


Figure 1. Timeline of vascular development. Adapted, with permission, from Hislop and Pierce ().


Figure 2. Arteriogram of a human lung obtained postmortem from a fetus (39 weeks gestation) showing distal vascularization. The arteries were injected with barium sulphate (mag × 0.75). Reprinted, with permission, from ().


Figure 3. Graph illustrating the relationship between PVR and volume. Adapted, with permission, from ().


Figure 4. Original three‐zone model proposed by West et al., () to illustrate the regional heterogeneity in blood flow. Within each of the three zones, the behavior of the blood vessels is different, based on the relative magnitudes of pulmonary arterial, alveolar and venous pressures (Pa, PA, and Pv, respectively). In zone 1, PA is greater than Pa, occluding collapsible vessels and preventing flow. In zone 2, Pa is greater than PA, which exceeds Pv, such that blood flow is dictated by the Pa‐PA pressure gradient. In zone 3, both Pa and Pv exceed PA, and vessels are held open, allowing blood flow based on the Pa‐Pv pressure gradient. Reproduced, with permission, from West et al. ().


Figure 5. Effect of PEEP and no, or zero, end expiratory pressure on VR and CO. (A) Effect of PEEP on CO and VR if PEEP has no effects on venous return flow limitation. Points A and B represent effects of PEEP without changes in mean systemic pressure (Pms). Point C represents effect of PEEP with Pms compensation. (B) Effect of PEEP on CO and venous return if increased VR flow limitation (FL2) occurs with higher PEEP. Reprinted, with permission, from Luecke and Pelosi ().


Figure 6. Proposed mechanisms by which hypoxia caused pulmonary vasoconstriction. Reproduced, with permission, from Sylvester et al. ().


Figure 7. The lung‐on‐a‐chip microdevice. (A) Compartmentalized channels form an alveolar‐capillary barrier on a thin, porous, flexible membrane. Physiological breathing movements are mimicked by applying a vacuum to the side chambers, causing mechanical stretching of the membrane that forms the alveolar‐capillary barrier. (B) Cartoon illustrating the mechanical effects of inspiration in the living lung, where contraction of the diaphragm reduced pleural pressure (Pip), resulting in distension of alveoli and physical stretching of the alveolar‐capillary interface. (C) The three‐layer system forming parallel microchannels with a porous membrane. Scale bar, 200 μm. (D) After the three layers are bonded together, the membrane layers in the side channels are removed, producing two side chambers to which vacuum is applied to cause mechanical stretching. Scale bar, 200 μm. (E) Actual images of a lung‐on‐a‐chip device. Reproduced, with permission, from ().


Figure 8. Illustration of putative mechanisms involved in the pathogenesis of pulmonary hypertension. Abbreviations: 5‐HT, 5‐hydroxytryptamin; K‐ and Ca‐channels, potassium and calcium channels; AEC, alveolar epithelial cells; BMP, bone morphogenetic protein; cGMP, cyclic guanosine monophosphate; ECM, extracellular matrix; EGF, epidermal growth factor; EPC, endothelial progenitor cells; HIF, hypoxia inducible factor; MMPs, matrix metalloproteinases; NADPH, nicotinamide adenine dinucleotide phosphate; NO, nitric oxide; PDE, phosphodiesterase; PDGF, platelet‐derived growth factor; PGI2, prostaglandin I2; Rho‐Ki, Rho kinases; ROS, reactive oxygen species; sGC, soluble guanylate cyclase; TGF, transforming growth factor‐β; TK, tyrosine kinase; TKi, tyrosine kinase inhibitor; TRPC, transient receptor potential cation channels; VEGF, vascular endothelial growth factor. Reproduced, with permission, from Schermuly et al. ().


Figure 9. Drawing by Fredrick Ruysch detailing the bronchial circulation. Reproduced, with permission, from Mitzner ().
References
 1. Aaronson PI , Robertson TP , Knock GA , Becker S , Lewis TH , Snetkov V , Ward JP . Hypoxic pulmonary vasoconstriction: mechanisms and controversies. J Physiol 570: 53‐58, 2006.
 2. Abe K , Shimokawa H , Morikawa K , Uwatoku T , Oi K , Matsumoto Y , Hattori T , Nakashima Y , Kaibuchi K , Sueishi K , Takeshit A . Long‐term treatment with a Rho‐kinase inhibitor improves monocrotaline‐induced fatal pulmonary hypertension in rats. Circ Res 94: 385‐393, 2004.
 3. Abe K , Toba M , Alzoubi A , Ito M , Fagan KA , Cool CD , Voelkel NF , McMurtry IF , Oka M . Formation of plexiform lesions in experimental severe pulmonary arterial hypertension. Circulation 121: 2747‐2754, 2010.
 4. Abe T , Arakawa Y , Rajasekaran AK , Yu TH , Wada O . Interaction of atrial natriuretic peptide with its receptors in bovine lung membranes. J Biol Chem 270: 7672‐7678, 1995.
 5. Abman SH , Accurso FJ . Acute effects of partial compression of ductus arteriosus on fetal pulmonary circulation. Am J Physiol 257: H626‐H634, 1989.
 6. Abud EM , Maylor J , Undem C , Punjabi A , Zaiman AL , Myers AC , Sylvester JT , Semenza GL , Shimoda LA . Digoxin inhibits development of hypoxic pulmonary hypertension in mice. Proc Natl Acad Sci U S A 109: 1239‐1244, 2012.
 7. Adkison JB , Miller GT , Weber DS , Miyahara T , Ballard ST , Frost JR , Parker JC . Differential responses of pulmonary endothelial phenotypes to cyclical stretch. Microvasc Res 71: 175‐184, 2006.
 8. Adnot S , Andrivet P , Chabrier PE , Piquet J , Plas P , Braquet P , Roudot‐Thoraval F , Brun‐Buisson C . Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion. J Clin Invest 83: 986‐993, 1989.
 9. Adnot S , Cigarini I , Herigault R , Harf A . Effects of substance P and calcitonin gene‐related peptide on the pulmonary circulation. J Appl Physiol 70: 1707‐1712, 1991.
 10. Aldred MA , Vijayakrishnan J , James V , Soubrier F , Gomez‐Sanchez MA , Martensson G , Galie N , Manes A , Corris P , Simonneau G , Humbert M , Morrell NW , Trembath RC . BMPR2 gene rearrangements account for a significant proportion of mutations in familial and idiopathic pulmonary arterial hypertension. Hum Mutat 27: 212‐213, 2006.
 11. Allen KM , Wharton J , Polak JM , Haworth SG . A study of nerves containing peptides in the pulmonary vasculature of healthy infants and children and of those with pulmonary hypertension. Brit Heart J 62: 353‐360, 1989.
 12. Altemeier WA , McKinney S , Krueger M , Glenny RW . Effect of posture on regional gas exchange in pigs. J Appl Physiol 97: 2104‐2111, 2004.
 13. Alvarez DF , King JA , Weber D , Addison E , Liedtke W , Townsley MI . Transient receptor potential vanilloid 4‐mediated disruption of the alveolar septal barrier: A novel mechanism of acute lung injury. Circ Res 99: 988, 2006.
 14. Alzoubi A , Toba M , Abe K , O'Neill KD , Rocic P , Fagan KA , McMurtry IF , Oka M . Dehydroepiandrosterone restores right ventricular structure and function in rats with severe pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 304: H1708‐H1718, 2013.
 15. Amis TC , Jones HA , Hughes JM . Effect of posture on inter‐regional distribution of pulmonary perfusion and VA/Q ratios in man. Resp Physiol 56: 169‐182, 1984.
 16. Anand‐Srivastava MB , Trachte GJ . Atrial natriuretic factor receptors and signal transduction mechanisms. Pharmacol Rev 45: 455‐497, 1993.
 17. Anderson L , Lowery JW , Frank DB , Novitskaya T , Jones M , Mortlock DP , Chandler RL , de Caestecker MP . Bmp2 and Bmp4 exert opposing effects in hypoxic pulmonary hypertension. Am J Physiol Regul Integr Comp Physiol 298: R833‐R842, 2010.
 18. Archer SL , Gomberg‐Maitland M , Maitland ML , Rich S , Garcia JG , Weir EK . Mitochondrial metabolism, redox signaling, and fusion: a mitochondria‐ROS‐HIF‐1α‐Kv1.5 O2‐sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol Heart Circ Physiol 294: H570‐H578, 2008.
 19. Archer SL , Huang J , Henry T , Peterson D , Weir EK . A redox‐based O2 sensor in rat pulmonary vasculature. Circ Res 73: 1100‐1112, 1993.
 20. Archer SL , Reeve HL , Michelakis E , Puttagunta L , Waite R , Nelson DP , Dinauer MC , Weir EK . O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase. Proc Nat Acad Sci 96: 7944‐7949, 1999.
 21. Archer SL , Tolins JP , Raij L , Weir EK . Hypoxic pulmonary vasoconstriction is enhanced by inhibition of the synthesis of an endothelium derived relaxing factor. Biochem Biophys Res Commun 164: 1198‐1205, 1989.
 22. Arias‐Stella J , Saldana M . The terminal portion of the pulmonary arterial tree in people native to high altitudes. Circulation 28: 915‐925, 1963.
 23. Asikainen TM , Ahmad A , Schneider BK , White CW . Effect of preterm birth on hypoxia‐inducible factors and vascular endothelial growth factor in primate lungs. Pediatric Pulm 40: 538‐546, 2005.
 24. Atlas S , Maack T . Atrial natriuretic factor. Compr Physiol (Suppl 25): 1577‐1673, 2011.
 25. Austin ED , Loyd JE . The genetics of pulmonary arterial hypertension. Circ Res 115: 189‐202, 2014.
 26. Bächler P , Pinochet N , Sotelo J , Crelier G , Irarrazaval P , Tejos C , Uribe SC . Assessment of normal flow patterns in the pulmonary circulation by using 4D magnetic resonance velocity mapping. Magn Reson Imaging 31: 178‐188.
 27. Badesch DB , Champion HC , Sanchez MA , Hoeper MM , Loyd JE , Manes A , McGoon M , Naeije R , Olschewski H , Oudiz RJ , Torbicki A . Diagnosis and assessment of pulmonary arterial hypertension. J Am Col Cardiol 54: S55‐S66, 2009.
 28. Baile EM . The anatomy and physiology of the bronchial circulation. J Aerosol Med 9: 1‐6, 1996.
 29. Ball MK , Waypa GB , Mungai PT , Nielsen JM , Czech L , Dudley VJ , Beussink L , Dettman RW , Berkelhamer SK , Steinhorn RH , Shah SJ , Schumacker PT . Regulation of hypoxia‐induced pulmonary hypertension by vascular smooth muscle HIF‐1a. Am J Respir Crit Care Med 189: 314‐324, 2013.
 30. Banasova A , Maxova H , Hampl V , Vizek M , Povysilova V , Novotna J , Vajnerova O , Hnilickova O , Herget J . Prevention of mast cell degranulation by disodium cromoglycate attenuates the development of hypoxic pulmonary hypertension in rats exposed to chronic hypoxia. Respiration 76: 102‐107, 2008.
 31. Barberà JA , Riverola A , Roca J , Ramirez J , Wagner PD , Ros D , Wiggs BR , Rodriguez‐Roisin R . Pulmonary vascular abnormalities and ventilation‐perfusion relationships in mild chronic obstructive pulmonary disease. Am J Resp Crit Care Med 149: 423‐429, 1994.
 32. Barer GR . The effect of catecholamine blocking and depleting agents on the changes in the pulmonary circulation caused by hypoxia and hypercapnia. J Physiol 186: 97P‐99P, 1966.
 33. Barman SA , Ardell JL , Parker JC , Perry ML , Taylor AE . Pulmonary and systemic blood flow contributions to upper airways in canine lung. Am J Physiol 255: H1130‐H1135, 1988.
 34. Barman SA , Pauly JR , Isales CM . Canine pulmonary vasoreactivity to serotonin: Role of protein kinase C and tyrosine kinase. Am J Physiol 272: H740‐H747, 1997.
 35. Barnard JW , Wilson PS , Moore TM , Thompson WJ , Taylor AE . Effect of nitric oxide and cyclooxygenase products on vascular resistance in dog and rat lungs. J Appl Physiol 74: 2940‐2948, 1993.
 36. Barnes PJ , Liu SF . Regulation of pulmonary vascular tone. Pharmacol Rev 47: 87‐131, 1995.
 37. Baudouin SV , Messent M , Evans TW . Effect of Intralipid on hypoxic and angiotensin‐II induced pulmonary vasoconstriction in the isolated rat lung. Crit Care Med 22: 1964‐1968, 1994.
 38. Bauer NR , Moore TM , McMurtry IF . Rodent models of PAH: Are we there yet? Am J Physiol Lung Cell Mol Physiol 293: L580‐L582, 2007.
 39. Baumgartner WA, Jr ., Jaryszak EM , Peterson AJ , Presson RG, Jr ., Wagner WW, Jr . Heterogeneous capillary recruitment among adjoining alveoli. J Appl Physiol (1985) 95: 469‐476, 2003.
 40. Beall CM . Tibetan and Andean contrasts in adaptation to high‐altitude hypoxia. Adv Exp Med Biol 475: 63‐74, 2000.
 41. Beall CM . Tibetan and Andean patterns of adaptation to high‐altitude hypoxia. Human Biol 72: 201‐228, 2000.
 42. Beall CM , Cavalleri GL , Deng L , Elston RC , Gao Y , Knight J , Li C , Li JC , Liang Y , McCormack M , Montgomery HE , Pan H , Robbins PA , Shianna KV , Tam SC , Tsering N , Veeramah KR , Wang W , Wangdui P , Weale ME , Xu Y , Xu Z , Yang L , Zaman MJ , Zeng C , Zhang L , Zhang X , Zhaxi P , Zheng YT . Natural selection on EPAS1 (HIF2a) associated with low hemoglobin concentration in Tibetan highlanders. Proc Nat Acad Sci 107: 11459‐11464, 2010.
 43. Beall CM , Decker MJ , Brittenham GM , Kushner I , Gebremedhin A , Strohl KP . An Ethiopian pattern of human adaptation to high‐altitude hypoxia. Proc Nat Acad Sci U S A 99: 17215‐17218, 2002.
 44. Becker PM , Verin AD , Booth MA , Liu F , Birukova A , Garcia JG . Differential regulation of diverse physiological responses to VEGF in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol 281: L1500‐L1511, 2001.
 45. Beckers CM , Knezevic N , Valent ET , Tauseef M , Krishnan R , Rajendran K , Hardin CC , Aman J , van Bezu J , Sweetnam P , van Hinsbergh VW , Mehta D , van Nieuw Amerongen GP . ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension. Vascul Pharmacol 70: 45‐54, 2015.
 46. Behrman RE , Lees MH , Peterson EN , De Lannoy CW , Seeds AE . Distribution of the circulation in the normal and asphyxiated fetal primate. Am J Obstet Gyn 108: 956‐969, 1970.
 47. Belik J . The myogenic response of arterial vessels is increased in fetal pulmonary hypertension. Ped Res 37: 196‐201, 1995.
 48. Benjamin JJ , Murtagh PS , Proctor DF , Menkes HA , Permutt S . Pulmonary vascular interdependence in excised dog lobes. J Appl Physiol 37: 887‐894, 1974.
 49. Beppu H , Ichinose F , Kawai N , Jones RC , Yu PB , Zapol WM , Miyazono K , Li E , Bloch KD . BMPR‐II heterozygous mice have mild pulmonary hypertension and an impaired pulmonary vascular remodeling response to prolonged hypoxia. Am J Physiol Lung Cell Mol Physiol 287:L1241‐1247, 2004.
 50. Berg JT . Chronic hypoxia‐induced pulmonary hypertension does/does not lead to loss of pulmonary vasculature. J Appl Physiol 103: 1455, 2007.
 51. Beutner A . Ueber die strom‐und druckkrafte des blutes in der arteria pulmonalis. Z Rationelle Med 2: 97‐138, 1852.
 52. Bhatt AJ , Amin SB , Chess PR , Watkins RH , Maniscalco WM . Expression of vascular endothelial growth factor and Flk‐1 in developing and glucocorticoid‐treated mouse lung. Ped Res 47: 606‐613, 2000.
 53. Bhattacharya J , Matthay MA . Regulation and repair of the alveolar‐capillary barrier in acute lung injury. Annu Rev Physiol 75: 593‐615, 2013.
 54. Bhattacharya J , Nanjo S , Staub NC . Micropuncture measurement of lung microvascular pressure during 5‐HT infusion. J Appl Physiol 52: 634‐637, 1982.
 55. Bhattacharya JC . Interpreting the lung microvascular filtration coefficient. Am J Physiol Lung Cell Mol Physiol 293: L9‐L10, 2007.
 56. Biaggioni I , King LS , Enayat N , Robertson D , Newman JH . Adenosine produces pulmonary vasoconstriction in sheep. Evidence for thromboxane A2/prostaglandin endoperoxide‐receptor activation. Circ Res 65: 1516‐1525, 1989.
 57. Bierer R , Nitta CH , Friedman J , Codianni S , de Frutos S , Dominguez‐Bautista JA , Howard TA , Resta TC , Bosc LV . NFATc3 is required for chronic hypoxia‐induced pulmonary hypertension in adult and neonatal mice. Am J Physiol Lung Cell Mol Physiol 301: L872‐L880, 2011.
 58. Bigham A , Bauchet M , Pinto D , Mao X , Akey JM , Mei R , Scherer SW , Julian CG , Wilson MJ , Lopez Herraez D , Brutsaert T , Parra EJ , Moore LG , Shriver MD . Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data. PLoS genetics 6: e1001116, 2010.
 59. Birks EK , Bousamra M , Presberg K , Marsh JA , Effros RM , Jacobs ER . Human pulmonary arteries dilate to 20‐HETE, an endogenous eicosanoid of lung tissue. The Am J Physiol 272: L823‐L829, 1997.
 60. Birukov KG , Zebda N , Birukova AA . Barrier enhancing signals in pulmonary edema. Compr Physiol 3: 429‐484, 2013.
 61. Birukov KGC . Small GTPases in mechanosensitive regulation of endothelial barrier. Microvasc Res 77: 46‐52, 2009.
 62. Bishop JM , Harris P , Segel N . The circulatory effects of bradykinin in normal subjects and patients with chronic bronchitis. Br J Pharmac Chemotherapy 25: 456‐469, 1965.
 63. Bishop R , McLeod D , McIlveen S , Blake R , Gunther R , Davis J , Talken L , Cottee D , Quail A , Parsons G , White S . Effects of graded exercise on bronchial blood flow and airway dimensions in sheep. Pulm Pharmacol Thera 20: 178‐189, 2007.
 64. Blitzer ML , Loh E , Roddy MA , Stamler JS , Creager MA . Endothelium‐derived nitric oxide regulates systemic and pulmonary vascular resistance during acute hypoxia in humans. J Am Coll Cardiol 28: 591‐596, 1996.
 65. Boe J , Simonsson BG . Adrenergic receptors and sympathetic agents in isolated human pulmonary arteries. Eur J Respir Dis 61: 195‐202, 1980.
 66. Bogeski I , Kappl R , Kummerow C , Gulaboski R , Hoth M , Niemeyer BA . Redox regulation of calcium ion channels: chemical and physiological aspects. Cell Calcium 50: 407‐423, 2011.
 67. Bolton TB , Clapp LH . Endothelial‐dependent relaxant actions of carbachol and substance P in arterial smooth muscle. Br J Pharmacol 87: 713‐723, 1986.
 68. Bolz SS , Fisslthaler B , Pieperhoff S , De Wit C , Fleming I , Busse R , Pohl U . Antisense oligonucleotides against cytochrome P450 2C8 attenuate EDHF‐mediated Ca2+ changes and dilation in isolated resistance arteries. Faseb J 14: 255‐260, 2000.
 69. Bonderman D , Ghio S , Felix SB , Ghofrani HA , Michelakis E , Mitrovic V , Oudiz RJ , Boateng F , Scalise AV , Roessig L , Semigran MJ , Left Ventricular Systolic Dysfunction Associated With Pulmonary Hypertension Riociguat Trial Study Group. Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double‐blind, randomized, placebo‐controlled, dose‐ranging hemodynamic study. Circulation 128: 502‐511, 2013.
 70. Bonnet S , Belus A , Hyvelin JM , Roux E , Marthan R , Savineau JP . Effect of chronic hypoxia on agonist‐induced tone and calcium signaling in rat pulmonary artery. Am J Physiol Lung Cell Mol Physiol 281: L193‐L201, 2001.
 71. Bonnet S , Dumas‐de‐La‐Roque E , Begueret H , Marthan R , Fayon M , Dos Santos P , Savineau JP , Baulieu EE . Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension. Proc Natl Acad Sci U S A 100: 9488‐9493, 2003.
 72. Bonnet S , Michelakis ED , Porter CJ , Andrade‐Navarro MA , Thebaud B , Bonnet S , Haromy A , Harry G , Moudgil R , McMurtry MS , Weir EK , Archer SL . An abnormal mitochondrial‐hypoxia inducible factor‐1a‐Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: Similarities to human pulmonary arterial hypertension. Circulation 113: 2630‐2641, 2006.
 73. Bonnet S , Rochefort G , Sutendra G , Archer SL , Haromy A , Webster L , Hashimoto K , Bonnet SN , Michelakis ED . The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted. Proc Natl Acad Sci U S A 104: 11418‐11423, 2007.
 74. Bouwmeester JC , Belenkie I , Shrive NG , Tyberg JV . Partitioning pulmonary vascular resistance using the reservoir‐wave model. J Appl Physiol 115: 1838‐1845, 2013.
 75. Breuer J , Meschig R , Breuer HW , Arnold G . Effects of serotonin on the cardiopulmonary circulatory system with and without 5‐HT2‐receptor blockade by ketanserin. J Cardiovasc Pharmacol 7(Suppl 7): S64‐S66, 1985.
 76. Brimioulle S , Vachiery JL , Brichant JF , Delcroix M , Lejeune P , Naeije R . Sympathetic modulation of hypoxic pulmonary vasoconstriction in intact dogs. Cardiovasc Res 34: 384‐392, 1997.
 77. Broadley KJ , Maddock HL . P1‐purinoceptor‐mediated vasodilatation and vasoconstriction in hypoxia. J Auton Pharmacol 16: 363‐366, 1996.
 78. Broughton BR , Walker BR , Resta TC . Chronic hypoxia induces Rho kinase‐dependent myogenic tone in small pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 294: L797‐L806, 2008.
 79. Brower R , Wise RA , Hassapoyannes C , Bromberger‐Barnea B , Permutt S . Effect of lung inflation on lung blood volume and pulmonary venous flow. J Appl Physiol 58: 954‐963, 1985.
 80. Brusselmans K , Compernolle V , Tjwa M , Wiesener MS , Maxwell PH , Collen D , Carmeliet P . Heterozygous deficiency of hypoxia‐inducible factor‐2α protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. J Clin Invest 111: 1519‐1527, 2003.
 81. Burg ED , Remillard CV , Yuan JX . Potassium channels in the regulation of pulmonary artery smooth muscle cell proliferation and apoptosis: Pharmacotherapeutic implications. Br J Pharmacol 153(Suppl 1): S99‐S111, 2008.
 82. Burnstock G . Purinergic cotransmission. F1000 Biol Rep 1: 46, 2009.
 83. Burri PH . Structural aspects of postnatal lung development ‐ alveolar formation and growth. Biol Neonate 89: 313‐322, 2006.
 84. Burri PH , Hlushchuk R , Djonov V . Intussusceptive angiogenesis: Its emergence, its characteristics, and its significance. Dev Dynamics 231: 474‐488, 2004.
 85. Bushuev VI , Miasnikova GY , Sergueeva AI , Polyakova LA , Okhotin D , Gaskin PR , Debebe Z , Nekhai S , Castro OL , Prchal JT , Gordeuk VR . Endothelin‐1, vascular endothelial growth factor and systolic pulmonary artery pressure in patients with Chuvash polycythemia. Haematologica 91: 744‐749, 2006.
 86. Campbell AG , Dawes GS , Fishman AP , Hyman AI , Perks AM . The release of a bradykinin‐like pulmonary vasodilator substance in foetal and new‐born lambs. J Physiol 195: 83‐96, 1968.
 87. Cargill RI , Lipworth BJ . Acute effects of hypoxaemia and angiotensin II in the human pulmonary vascular bed. Pulm Pharmacol 7: 305‐310, 1994.
 88. Carlsson P , Mahlapuu M . Forkhead transcription factors: Key players in development and metabolism. Developmental biology 250: 1‐23, 2002.
 89. Carmeliet P , Ferreira V , Breier G , Pollefeyt S , Kieckens L , Gertsenstein M , Fahrig M , Vandenhoeck A , Harpal K , Eberhardt C , Declercq C , Pawling J , Moons L , Collen D , Risau W , Nagy A . Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380: 435‐439, 1996.
 90. Carvajal JA , Germain AM , Huidobro‐Toro JP , Weiner CP . Molecular mechanism of cGMP‐mediated smooth muscle relaxation. J Cell Physiol 184: 409‐420, 2000.
 91. Carvalho P , Anderson DK , Charan NB . Bronchial arterial imaging using helical computed tomography. Pulm Pharmacol Ther 20: 104‐108, 2007.
 92. Casey DB , Badejo AM , Dhaliwal JS , Sikora JL , Fokin A , Golwala NH , Greco AJ , Murthy SN , Nossaman BD , Hyman AL , Kadowitz PJ . Analysis of responses to the Rho‐kinase inhibitor Y‐27632 in the pulmonary and systemic vascular bed of the rat. Am J Physiol Heart Circ Physiol 299: H184‐H192, 2010.
 93. Cassin S . The role of eicosanoids and endothelium‐dependent factors in regulation of the fetal pulmonary circulation. J Lipid Med 6: 477‐485, 1993.
 94. Catravas JD , Buccafusco JJ , El Kashef H . Effects of acetylcholine in the pulmonary circulation of rabbits. J Pharmacol Exp Ther 231: 236‐241, 1984.
 95. Cauldwell EW , Siekert RG , Lininger RE, Anson BJ. The bronchial arteries; an anatomic study of 150 human cadavers. Surg Gynecol Obstet 86: 395‐412, 1948.
 96. Cech S . Adrenergic innervation of blood vessels in the lung of some mammals. Acta Anatomica 74: 169‐182, 1969.
 97. Chabot F , Mitchell JA , Gutteridge JM , Evans TW . Reactive oxygen species in acute lung injury. Eur Resp J 11: 745, 1998.
 98. Chandel NS , Schumacker PT . Cellular oxygen sensing by mitochondria: Old questions, new insight. J Appl Physiol 88: 1880‐1889, 2000.
 99. Charan NB , Carvalho P , Agostoni PG . On the purported discovery of the bronchial circulation by Leonardo da Vinci: A rebuttal. J Appl Physiol 76: 1836‐1838, 1994.
 100. Charan NB , Johnson SR , Lakshminarayan S , Thompson WH , Carvalho P . Nitric oxide and beta‐adrenergic agonist‐induced bronchial arterial vasodilation. J Appl Physiol 82: 686‐692, 1997.
 101. Charan NB , Turk GM , Dhand R . Gross and subgross anatomy of bronchial circulation in sheep. J Appl Physiol 57: 658‐664, 1984.
 102. Chen G , Yamamoto Y , Miwa K , Suzuki H . Hyperpolarization of arterial smooth muscle induced by endothelial humoral substances. Am J Physiol: Heart Circ Physiol 260: H1888‐H1892, 1991.
 103. Cheng DY , DeWitt BJ , Suzuki F , Neely CF , Kadowitz PJ . Adenosine A1 and A2 receptors mediate tone‐dependent responses in feline pulmonary vascular bed. Am J Physiol: Heart Circ Physiol 270: H200‐H207, 1996.
 104. Chetham PM , Babal P , Bridges JP , Moore TM , Stevens T . Segmental regulation of pulmonary vascular permeability by store‐operated Ca2+ entry. Am J Physiol 276: L41‐L50, 1999.
 105. Chettimada S , Gupte R , Rawat D , Gebb SA , McMurtry IF , Gupte SA . Hypoxia‐induced glucose‐6‐phosphate dehydrogenase overexpression and ‐activation in pulmonary artery smooth muscle cells: Implication in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 308: L287‐L300, 2015.
 106. Chettimada S , Rawat DK , Dey N , Kobelja R , Simms Z , Wolin MS , Lincoln TM , Gupte SA . Glc‐6‐PD and PKG contribute to hypoxia‐induced decrease in smooth muscle cell contractile phenotype proteins in pulmonary artery. Am J Physiol Lung Cell Mol Physiol 303: L64‐L74, 2012.
 107. Chi JT , Chang HY , Haraldsen G , Jahnsen FL , Troyanskaya OG , Chang DS , Wang Z , Rockson SG , van de Rijn M , Botstein D , Brown PO . Endothelial cell diversity revealed by global expression profiling. Proc Natl Acad Sci U S A 100: 10623‐10628, 2003.
 108. Cigarini I , Adnot S , Chabrier PE , Viossat I , Braquet P , Gaujour B . Pulmonary vasodilator responses to atrial natriuretic factor and sodium nitroprusside. J Appl Physiol 67: 2269‐2275, 1989.
 109. Cioffi DL , Lowe K , Alvarez DF , Barry C , Stevens T . TRPing on the lung endothelium: calcium channels that regulate barrier function. Antioxidants Redox Signal 11: 765, 2009.
 110. Ciuclan L , Bonneau O , Hussey M , Duggan N , Holmes AM , Good R , Stringer R , Jones P , Morrell NW , Jarai G , Walker C , Westwick J , Thomas M . A novel murine model of severe pulmonary arterial hypertension. Am J Resp Crit Care Med 184: 1171‐1182, 2012.
 111. Clark J , Alvarez DF , Alexeyev M , King JA , Huang L , Yoder MC , Stevens T . Regulatory role for nucleosome assembly protein‐1 in the proliferative and vasculogenic phenotype of pulmonary endothelium. Am J Physiol Lung Cell Mol Physiol 294: L431‐L439, 2008.
 112. Cogan JD , Pauciulo MW , Batchman AP , Prince MA , Robbins IM , Hedges LK , Stanton KC , Wheeler LA , Phillips JA, III , Loyd JE , Nichols WC . High frequency of BMPR2 exonic deletions/duplications in familial pulmonary arterial hypertension. Am J Resp Crit Care Med 174: 590‐598, 2006.
 113. Cogan JD , Vnencak‐Jones CL , Phillips JA, III , Lane KB , Wheeler LA , Robbins IM , Garrison G , Hedges LK , Loyd JE . Gross BMPR2 gene rearrangements constitute a new cause for primary pulmonary hypertension. Genet Med 7: 169‐174, 2005.
 114. Cogolludo A , Moreno L , Bosca L , Tamargo J , Perez‐Vizcaino F . Thromboxane A2‐induced inhibition of voltage‐gated K+ channels and pulmonary vasoconstriction: Role of protein kinase Czeta. Circ Res 93: 656‐663, 2003.
 115. Cohen ED , Tian Y , Morrisey EE . Wnt signaling: An essential regulator of cardiovascular differentiation, morphogenesis and progenitor self‐renewal. Development 135: 789‐798, 2008.
 116. Colen KL , Crisera CA , Rose MI , Connelly PR , Longaker MT , Gittes GK . Vascular development in the mouse embryonic pancreas and lung. J Pediat Surg 34: 781‐785, 1999.
 117. Compernolle V , Brusselmans K , Franco D , Moorman A , Dewerchin M , Collen D , Carmeliet P . Cardia bifida, defective heart development and abnormal neural crest migration in embryos lacking hypoxia‐inducible factor‐1α. Cardiovas Res 60: 569‐579, 2003.
 118. Conhaim RL , Staub NC . Reflection spectrophotometric measurement of O2 uptake in pulmonary arterioles of cats. J Appl Physiol 48: 848‐856, 1980.
 119. Cosby K , Partovi KS , Crawford JH , Patel RP , Reiter CD , Martyr S , Yang BK , Waclawiw MA , Zalos G , Xu X , Huang KT , Shields H , Kim‐Shapiro DB , Schechter AN , Cannon RO, III , Gladwin MT . Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 9: 1498‐1505, 2003.
 120. Cudkowicz L , Armstrong JB . Observations on the normal anatomy of the bronchial arteries. Thorax 6: 343‐358, 1951.
 121. Dahal BK , Kosanovic D , Kaulen C , Cornitescu T , Savai R , Hoffmann J , Reiss I , Ghofrani HA , Weissmann N , Kuebler WM , Seeger W , Grimminger F , Schermuly RT . Involvement of mast cells in monocrotaline‐induced pulmonary hypertension in rats. Respir Res 12: 60, 2011.
 122. Dallal MM , Chang SW . Evans blue dye in the assessment of permeability‐surface area product in perfused rat lungs. J Appl Physiol 77: 1030‐1035, 1994.
 123. Daly ID , Michel CC , Ramsay DJ , Waaler BA . Conditions governing the pulmonary vascular response to ventilation hypoxia and hypoxaemia in the dog. J Physiol 196: 351‐379, 1968.
 124. Davenport AP , O'Reilly G , Kuc RE . Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: Majority of the ETA sub‐type. Br J Pharmacol 114: 1110‐1116, 1995.
 125. Davie NJ , Schermuly RT , Weissmann N , Grimminger F , Ghofrani HA . The science of endothelin‐1 and endothelin receptor antagonists in the management of pulmonary arterial hypertension: current understanding and future studies. Eur J Clin Invest 39(Suppl 2): 38‐49, 2009.
 126. Davies RJ , Morrell NW . Molecular mechanisms of pulmonary arterial hypertension: Role of mutations in the bone morphogenetic protein type II receptor. Chest 134: 1271‐1277, 2008.
 127. Davis S , Yancopoulos GD . The angiopoietins: Yin and Yang in angiogenesis. Curr Top Microbiol Immunol 237: 173‐185, 1999.
 128. Dawes GS , Mott JC . The vascular tone of the foetal lung. J Physiol 164: 465‐477, 1962.
 129. Dawson CA . Role of pulmonary vasomotion in physiology of the lung. Physiol Rev 64: 544‐616, 1984.
 130. DebRoy A , Vogel SM , Soni D , Sundivakkam PC , Malik AB , Tiruppathi C . Cooperative signaling via transcription factors NF‐κB and AP1/c‐Fos mediates endothelial cell STIM1 expression and hyperpermeability in response to endotoxin. J Biol Chem 289(35): 24188‐24201, 2014.
 131. Deffebach ME . Lung mechanical effects on the bronchial circulation. Eur Resp J Supplement 12: 586s‐590s, 1990.
 132. Deffebach ME , Agostoni P , Kirk W , Lakshminarayan S . Pulmonary artery infusion of prostacyclin increases lobar bronchial blood flow. Resp Physiol 77: 147‐156, 1989.
 133. Deffebach ME , Charan NB , Lakshminarayan S , Butler J . The bronchial circulation. Small, but a vital attribute of the lung. Am Rev Resp Dis 135: 463‐481, 1987.
 134. Del Vecchio PJ , Siflinger‐Birnboim A , Belloni PN , Holleran LA , Lum H , Malik AB . Culture and characterization of pulmonary microvascular endothelial cells. In Vitro Cell Dev Biol 28A: 711‐715, 1992.
 135. Delaney C , Gien J , Grover TR , Roe G , Abman SH . Pulmonary vascular effects of serotonin and selective serotonin reuptake inhibitors in the late‐gestation ovine fetus. Am J Physiol Lung Cell Mol Physiol 301: L937‐L944, 2011.
 136. deMello DE , Reid LM . Embryonic and early fetal development of human lung vasculature and its functional implications. Pediat Dev Path 3: 439‐449, 2000.
 137. deMello DE , Sawyer D , Galvin N , Reid LM . Early fetal development of lung vasculature. Am J Resp Cell Mol Bio 16: 568‐581, 1997.
 138. Deng Z , Morse JH , Slager SL , Cuervo N , Moore KJ , Venetos G , Kalachikov S , Cayanis E , Fischer SG , Barst RJ , Hodge SE , Knowles JA . Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor‐II gene. Am J Hum Genet 67: 737‐744, 2000.
 139. Dhaliwal JS , Casey DB , Greco AJ , Badejo AM , Gallen TB , Murthy SN , Nossaman BD , Hyman AL , Kadowitz PJ . Rho kinase and Ca2+ entry mediate increased pulmonary and systemic vascular resistance in L‐NAME‐treated rats. Am J Physiol Lung Cell Mol Physiol 293: L1306‐L1313, 2007.
 140. Dhillon GS , Zamora MR , Roos JE , Sheahan D , Sista RR , Van der Starre P , Weill D , Nicolls MR . Lung transplant airway hypoxia: A diathesis to fibrosis? Am J Resp Crit Care Med 182: 230‐236, 2010.
 141. Dib H , Tamby MC , Bussone G , Regent A , Berezne A , Lafine C , Broussard C , Simonneau G , Guillevin L , Witko‐Sarsat V , Humbert M , Mouthon L . Targets of anti‐endothelial cell antibodies in pulmonary hypertension and scleroderma. Eur Respir J 39: 1405‐1414, 2012.
 142. Dickson MC , Martin JS , Cousins FM , Kulkarni AB , Karlsson S , Akhurst RJ . Defective haematopoiesis and vasculogenesis in transforming growth factor‐b 1 knock out mice. Development 121: 1845‐1854, 1995.
 143. Domkowski PW , Cockerham JT , Kot PA , Myers JL , Wallace RB , Hopkins RA . The role of N omega‐nitro‐L‐arginine in modulation of pulmonary vascular tone in the maturing newborn pig. J Thorac Cardiovasc Surg 110: 1486‐1492, 1995.
 144. Du HL , Yamada Y , Orii R , Suzuki S , Sawamura S , Suwa K , Hanaoka K . Beneficial effects of the prone position on the incidence of barotrauma in oleic acid‐induced lung injury under continuous positive pressure ventilation. Acta Anaesthesiol Scand 41: 701‐707, 1997.
 145. Du L , Sullivan CC , Chu D , Cho AJ , Kido M , Wolf PL , Yuan JX , Deutsch R , Jamieson SW , Thistlethwaite PA . Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 348: 500‐509, 2003.
 146. Dudek SM , Garcia JG . Cytoskeletal regulation of pulmonary vascular permeability. J Appl Physiol 91: 1487‐1500, 2001.
 147. Duluc L , Wojciak‐Stothard B . Rho GTPases in the regulation of pulmonary vascular barrier function. Cell Tissue Res 355: 675‐685, 2014.
 148. Dumas de La Roque E , Savineau JP , Metivier AC , Billes MA , Kraemer JP , Doutreleau S , Jougon J , Marthan R , Moore N , Fayon M , Baulieu EE , Dromer C . Dehydroepiandrosterone (DHEA) improves pulmonary hypertension in chronic obstructive pulmonary disease (COPD): A pilot study. Annales d'endocrinologie 73: 20‐25, 2012.
 149. Duran WN , Breslin JW , Sanchez FACP . The NO cascade, eNOS location, and microvascular permeability. Cardiovas Res 87: 254‐261, 2010.
 150. Eddahibi S , Fabre V , Boni C , Martres MP , Raffestin B , Hamon M , Adnot S . Induction of serotonin transporter by hypoxia in pulmonary vascular smooth muscle cells. Relationship with the mitogenic action of serotonin. Circ Res 84:329‐336, 1999.
 151. El Chami H , Hassoun PM . Inflammatory mechanisms in the pathogenesis of pulmonary arterial hypertension. Compr Physiol 1: 1929‐1941, 2011.
 152. El‐Bermani AW , Bloomquist EI , Montvilo JA . Distribution of pulmonary cholinergic nerves in the rabbit. Thorax 37: 703‐710, 1982.
 153. El‐Kashef H , Elmazar MM , Al‐Shabanah OA , Al‐Bekairi AM . Effect of adenosine on pulmonary circulation of rabbits. Gen Pharmacol 32: 307‐313, 1999.
 154. Elliott CG . Genetics of pulmonary arterial hypertension: Current and future implications. Semin Respir Crit Care Med 26: 365‐371, 2005.
 155. Elliott FM , Reid L . Some new facts about the pulmonary artery and its branching pattern. Clin Radiol 16: 193‐198, 1965.
 156. Ema M , Taya S , Yokotani N , Sogawa K , Matsuda Y , Fujii‐Kuriyama Y . A novel bHLH‐PAS factor with close sequence similarity to hypoxia‐inducible factor 1α regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Nat Acad Sci U S A 94: 4273‐4278, 1997.
 157. Emery CJ , Teng GQ , Liu X , Barer GR . Vasoreactions to acute hypoxia, whole lungs and isolated vessels compared: modulation by NO. Resp Physiol Neurobiol 134: 115‐129, 2003.
 158. Emmanouilides GC , Moss AJ , Duffie ER, Jr. , Adams FH . Pulmonary arterial pressure changes in human newborn infants from birth to 3 days of age. J Pediat 65: 327‐333, 1964.
 159. Fadel E , Wijtenburg E , Michel R , Mazoit JX , Bernatchez R , Decante B , Sage E , Mazmanian M , Herve P . Regression of the systemic vasculature to the lung after removal of pulmonary artery obstruction. Am J Resp Crit Care Med 173: 345‐349, 2006.
 160. Fagan KA , Oka M , Bauer NR , Gebb SA , Ivy DD , Morris KG , McMurtry IF . Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho‐kinase. Am J Physiol Lung Cell Mol Physiol 287: L656‐L664, 2004.
 161. Farhi L . Ventilation‐perfusion relationships. Compr Physiol (Suppl 13): 199‐215, 2011.
 162. Feletou M , Vanhoutte PM . Endothelium‐dependent hyperpolarization of canine coronary smooth muscle. Br J Pharmacol 93: 515‐524, 1988.
 163. Feng CJ , Cheng DY , Kaye AD , Kadowitz PJ , Nossaman BD . Influence of N omega‐nitro‐L‐arginine methyl ester, LY83583, glybenclamide and L158809 on pulmonary circulation. Eur J Pharmacol 263: 133‐140, 1994.
 164. Fessler HE . Heart‐lung interactions: Applications in the critically ill. Eur Respir J 10: 226‐237, 1997.
 165. Fijalkowska I , Xu W , Comhair SA , Janocha AJ , Mavrakis LA , Krishnamachary B , Zhen L , Mao T , Richter A , Erzurum SC , Tuder RM . Hypoxia inducible‐factor1α regulates the metabolic shift of pulmonary hypertensive endothelial cells. Am J Pathol 176: 1130‐1138, 2010.
 166. Fike CD , Kaplowitz MR , Pfister SL . Arachidonic acid metabolites and an early stage of pulmonary hypertension in chronically hypoxic newborn pigs. Am J Physiol Lung Cell Mol Physiol 284: L316‐L323, 2003.
 167. Firth AL , Choi I‐W , Park WS . Animal models of pulmonary hypertension: Rho kinase inhibition. Prog Biophys Mol Biol 109: 67‐75, 2012.
 168. Fischer A , Mundel P , Mayer B , Preissler U , Philippin B , Kummer W . Nitric oxide synthase in guinea pig lower airway innervation. Neurosci Let 149: 157‐160, 1993.
 169. Fischer LG , Honemann CW , Patrie JT , Durieux ME , Rich GF . Ropivacaine attenuates pulmonary vasoconstriction induced by thromboxane A2 analogue in the isolated perfused rat lung. Reg Anesth Pain Med 25: 187‐194, 2000.
 170. Fisher AB . The serpentine path to a novel mechanism‐based inhibitor of acute inflammatory lung injury. J Appl Physiol 116:1521‐1530, 2014.
 171. Fisher AW . The intrinsic innervation of the pulmonary vessels. Acta Anatomica 60: 481‐496, 1965.
 172. Fishman A . Pulmonary Circulation. Comp Physiol 93‐165, 2011.
 173. Fishman AP . Autonomic vasomotor tone in the pulmonary circulation. Anesthesiology 45: 1‐2, 1976.
 174. Fishman AP . The pulmonary circulation. JAMA 239: 1299‐1301, 1978.
 175. Fisslthaler B , Fleming I , Busse R . EDHF: A cytochrome P450 metabolite in coronary arteries. Semin Perinatol 24: 15‐19, 2000.
 176. Fleming I . DiscrEET regulators of homeostasis: Epoxyeicosatrienoic acids, cytochrome P450 epoxygenases and vascular inflammation. Trends Pharmacol Sci 28: 448‐452, 2007.
 177. Fleming I , Busse R . Endothelium‐derived epoxyeicosatrienoic acids and vascular function. Hyperten 47: 629‐633, 2006.
 178. Fong GH , Rossant J , Gertsenstein M , Breitman ML . Role of the Flt‐1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nat 376: 66‐70, 1995.
 179. Formenti F , Beer PA , Croft QP , Dorrington KL , Gale DP , Lappin TR , Lucas GS , Maher ER , Maxwell PH , McMullin MF , O'Connor DF , Percy MJ , Pugh CW , Ratcliffe PJ , Smith TG , Talbot NP , Robbins PA . Cardiopulmonary function in two human disorders of the hypoxia‐inducible factor (HIF) pathway: von Hippel‐Lindau disease and HIF‐2α gain‐of‐function mutation. FASEB J 25: 2001‐2011, 2011.
 180. Fraidenburg D , Yuan J . Current and future therapeutic targets for pulmonary arterial hypertension. High Alt Med Biol 14: 134‐143, 2013.
 181. Frank DB , Abtahi A , Yamaguchi DJ , Manning S , Shyr Y , Pozzi A , Baldwin HS , Johnson JE , de Caestecker MP . Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic pulmonary hypertension. Circ Res 97: 496‐504, 2005.
 182. Frank DB , Lowery J , Anderson L , Brink M , Reese J , de Caestecker M . Increased susceptibility to hypoxic pulmonary hypertension in Bmpr2 mutant mice is associated with endothelial dysfunction in the pulmonary vasculature. Am J Physiol Lung Cell Mol Physiol 294:L98‐109, 2008.
 183. Frantz E , Soifer SJ , Clyman RI , Heymann MA . Bradykinin produces pulmonary vasodilation in fetal lambs: Role of prostaglandin production. J Appl Physiol 67: 1512‐1517, 1989.
 184. Frid MG , Brunetti JA , Burke DL , Carpenter TC , Davie NJ , Reeves JT , Roedersheimer MT , van Rooijen N , Stenmark KR . Hypoxia‐induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage. Am J Path 168: 659‐669, 2006.
 185. Fujimoto K , Sakai A , Yoshikawa S , Shinozaki S , Matsuzawa Y , Kubo K , Kobayashi T , Ueda G , Sekiguchi M , Voelkel NF . Effect of cyclic guanosine monophosphate on hypoxic and angiotensin‐II‐induced pulmonary vasoconstriction. Lung 168: 333‐343, 1990.
 186. Fujita H , Fukumoto Y , Saji K , Sugimura K , Demachi J , Nawata J , Shimokawa H . Acute vasodilator effects of inhaled fasudil, a specific Rho‐kinase inhibitor, in patients with pulmonary arterial hypertension. Heart Vessels 25: 144‐149, 2010.
 187. Fukumoto Y , Matoba T , Ito A , Tanaka H , Kishi T , Hayashidani S , Abe K , Takeshita A , Shimokawa H . Acute vasodilator effects of a Rho‐kinase inhibitor, fasudil, in patients with severe pulmonary hypertension. Heart 91: 391‐392, 2005.
 188. Fukuroda T , Kobayashi M , Ozaki S , Yano M , Miyauchi T , Onizuka M , Sugishita Y , Goto K , Nishikibe M . Endothelin receptor subtypes in human versus rabbit pulmonary arteries. J Appl Physiol 76: 1976‐1982, 1994.
 189. Fullerton DA , Kirson LE , Jones SD , McIntyre RC, Jr . Adenosine is a selective pulmonary vasodilator in cardiac surgical patients. Chest 109: 41‐46, 1996.
 190. Fuloria M , Eckman DM , Leach DA , Aschner JL . 20‐hydroxyeicosatetraenoic acid is a vasoconstrictor in the newborn piglet pulmonary microcirculation. Am J Physiol Lung Cell Mol Physiol 287: L360‐L365, 2004.
 191. Fung YC , Sobin SS . Pulmonary alveolar blood flow. Circ Res 30: 470‐490, 1972.
 192. Fung YC , Zhuang FY . An analysis of the sluicing gate in pulmonary blood flow. J Biomech Eng 108: 175‐182, 1986.
 193. Furchgott RF , Bhadrakom S . Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs. J Pharm Exp Ther 108: 129‐143, 1953.
 194. Gaar KA, Jr. , Taylor AE , Owens LJ , Guyton AC . Pulmonary capillary pressure and filtration coefficient in the isolated perfused lung. Am J Physiol 213: 910‐914, 1967.
 195. Gale DP , Harten SK , Reid CD , Tuddenham EG , Maxwell PH . Autosomal dominant erythrocytosis and pulmonary arterial hypertension associated with an activating HIF2 α mutation. Blood 112: 919‐921, 2008.
 196. Galie N , Brundage BH , Ghofrani HA , Oudiz RJ , Simonneau G , Safdar Z , Shapiro S , White RJ , Chan M , Beardsworth A , Frumkin L , Barst RJ , Pulmonary Arterial H, Response to Tadalafil Study G. Tadalafil therapy for pulmonary arterial hypertension. Circulation 119: 2894‐2903, 2009.
 197. Galie N , Hoeper MM , Humbert M , Torbicki A , Vachiery JL , Barbera JA , Beghetti M , Corris P , Gaine S , Gibbs JS , Gomez‐Sanchez MA , Jondeau G , Klepetko W , Opitz C , Peacock A , Rubin L , Zellweger M , Simonneau G . Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 30: 2493‐2537, 2009.
 198. Gambone LM , Murray PA , Flavahan NA . Synergistic interaction between endothelium‐derived NO and prostacyclin in pulmonary artery: Potential role for K+ ATP channels. Br J Pharmacol 121: 271‐279, 1997.
 199. Gan CT‐J , Lankhaar J‐W , Westerhof N , Marcus JT , Becker A , Twisk JWR , Boonstra A , Postmus PE , Vonk‐Noordegraaf A . Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension. Chest 132:1906‐1912, 2007.
 200. Gandhirajan RK , Meng S , Chandramoorthy HC , Mallilankaraman K , Mancarella S , Gao H , Razmpour R , Yang XF , Houser SR , Chen J , Koch WJ , Wang H , Soboloff J , Gill DL , Madesh M . Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide‐induced vascular inflammation. J Clin Invest 123: 887, 2013.
 201. Gangopahyay A , Oran M , Bauer EM , Wertz JW , Comhair SA , Erzurum SC , Bauer PM . Bone morphogenetic protein receptor II is a novel mediator of endothelial nitric‐oxide synthase activation. J Biol Chem 286: 33134‐33140, 2011.
 202. Gao Y , Raj JU . Regulation of the pulmonary circulation in the fetus and newborn. Physiol Rev 90: 1291‐1335, 2010.
 203. Gao Y , Raj JU . Hypoxic pulmonary hypertension of the newborn. Compr Physiol 1: 61‐79, 2011.
 204. Gatherer D , Ten Dijke P , Baird DT , Akhurst RJ . Expression of TGF‐beta isoforms during first trimester human embryogenesis. Development 110: 445‐460, 1990.
 205. Gattinoni L , Pesenti A , Carlesso E . Body position changes redistribute lung computed‐tomographic density in patients with acute respiratory failure: Impact and clinical fallout through the following 20 years. Inten Care Med 39: 1909‐1915, 2013.
 206. Gauthier KM , Edwards EM , Falck JR , Reddy DS , Campbell WB . 14,15‐Epoxyeicosatrienoic acid represents a transferable endothelium‐dependent relaxing factor in bovine coronary arteries. Hypertension 45: 666‐671, 2005.
 207. Gavard J , Gutkind JS . VEGF controls endothelial‐cell permeability by promoting the beta‐arrestin‐dependent endocytosis of VE‐cadherin. Nat Cell Biol 8: 1223‐1234, 2006.
 208. Gebb S , Stevens T . On lung endothelial cell heterogeneity. Microvasc Res 68: 1‐12, 2004.
 209. Gebb SA , Shannon JM . Tissue interactions mediate early events in pulmonary vasculogenesis. Dev Dynam 217: 159‐169, 2000.
 210. Gehr P , Bachofen M , Weibel ER . The normal human lung: Ultrastructure and morphometric estimation of diffusion capacity. Resp Physiol 32: 121‐140, 1978.
 211. Gerber JG , Voelkel N , Nies AS , McMurtry IF , Reeves JT . Moderation of hypoxic vasoconstriction by infused arachidonic acid: Role of PGI2. J Appl Physiol 49: 107‐112, 1980.
 212. Gerthoffer WT . Mechanisms of vascular smooth muscle cell migration. Circ Res 100: 607‐621, 2007.
 213. Ghofrani HA , D'Armini AM , Grimminger F , Hoeper MM , Jansa P , Kim NH , Mayer E , Simonneau G , Wilkins MR , Fritsch A , Neuser D , Weimann G , Wang C , Group C‐S . Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Eng J Med 369: 319‐329, 2013.
 214. Ghofrani HA , Galie N , Grimminger F , Grunig E , Humbert M , Jing ZC , Keogh AM , Langleben D , Kilama MO , Fritsch A , Neuser D , Rubin LJ , Group P‐S . Riociguat for the treatment of pulmonary arterial hypertension. N Eng J Med 369: 330‐340, 2013.
 215. Girgis RE , Li D , Zhan X , Garcia JG , Tuder RM , Hassoun PM , Johns RA . Attenuation of chronic hypoxic pulmonary hypertension by simvastatin. Am J Physiol Heart Circ Physiol 285: H938‐H945, 2003.
 216. Girgis RE , Mozammel S , Champion HC , Li D , Peng X , Shimoda L , Tuder RM , Johns RA , Hassoun PM . Regression of chronic hypoxic pulmonary hypertension by simvastatin. Am J Physiol Lung Cell Mol Physiol 292: L1105‐L1110, 2007.
 217. Glenny R , Robertson HT . Distribution of perfusion. Compr Physiol 1: 245‐262, 2011.
 218. Glenny RW , Bernard S , Robertson HT , Hlastala MP . Gravity is an important but secondary determinant of regional pulmonary blood flow in upright primates. J Appl Physiol 86: 623‐632, 1999.
 219. Glenny RW , Robertson HT . A computer simulation of pulmonary perfusion in three dimensions. J Appl Physiol 79: 357‐369, 1995.
 220. Glenny RW , Robertson HT . Determinants of pulmonary blood flow distribution. Compr Physiol 1: 39‐59, 2011.
 221. Glover GH , Newsom IE . Brisket disease: dropsy of high altitudes. Colo Agric Exp Station 204: 3‐24, 1915.
 222. Goll HM , Nyhan DP , Geller HS , Murray PA . Pulmonary vascular responses to angiotensin II and captopril in conscious dogs. J Appl Physiol 61: 1552‐1559, 1986.
 223. Golovina VA , Platoshyn O , Bailey CL , Wang J , Limsuwan A , Sweeney M , Rubin LJ , Yuan JX . Upregulated TRP and enhanced capacitative Ca2+ entry in human pulmonary artery myocytes during proliferation. Am J Physiol Heart Circ Physiol 280: H746‐H755, 2001.
 224. Gomberg‐Maitland M , Bull TM , Saggar R , Barst RJ , Elgazayerly A , Fleming TR , Grimminger F , Rainisio M , Stewart DJ , Stockbridge N , Ventura C , Ghofrani AH , Rubin LJ . New trial designs and potential therapies for pulmonary artery hypertension. J Am Col Card 62: D82‐D91, 2013.
 225. Goncharov DA , Kudryashova TV , Ziai H , Ihida‐Stansbury K , DeLisser H , Krymskaya VP , Tuder RM , Kawut SM , Goncharova EA . Mammalian target of rapamycin complex 2 (mTORC2) coordinates pulmonary artery smooth muscle cell metabolism, proliferation, and survival in pulmonary arterial hypertension. Circulation 129: 864‐874, 2014.
 226. Goncharova EA . mTOR and vascular remodeling in lung diseases: Current challenges and therapeutic prospects. FASEB J 27: 1796‐1807, 2013.
 227. Gonzales‐Luis G , Fletcher AJ , Moreno L , Perez‐Vizcaino F , Blanco CE , Villamor E . Nitric oxide‐mediated nonadrenergic noncholinergic relaxation of piglet pulmonary arteries decreases with postnatal age. J Physiol Pharmacol 58: 45‐56, 2007.
 228. Gordon JB , Tod ML . Effects of N omega‐nitro‐L‐arginine on total and segmental vascular resistances in developing lamb lungs. J Appl Physiol 75: 76‐85, 1993.
 229. Gottlieb JE , Peake MD , Sylvester JT . Adenosine and hypoxic pulmonary vasodilation. Am J Physiol Heart Circ Physiol 247: H541‐H547, 1984.
 230. Graham R , Skoog C , Oppenheimer L , Rabson J , Goldberg HS . Critical closure in the canine pulmonary vasculature. Circ Res 50: 566‐572, 1982.
 231. Green DE , Murphy TC , Kang BY , Kleinhenz JM , Szyndralewiez C , Page P , Sutliff RL , Hart CM . The Nox4 inhibitor GKT137831 attenuates hypoxia‐induced pulmonary vascular cell proliferation. Am J Respir Cell Mol Biol 47: 718‐726, 2012.
 232. Groenman F , Rutter M , Caniggia I , Tibboel D , Post M . Hypoxia‐inducible factors in the first trimester human lung. J Histochem Cytochem 55: 355‐363, 2007.
 233. Grover RF , Wagner WW , McMurtry IF , Reeves JT . Pulmonary Circulation. Compr Physiol (Suppl 8): 103‐136, 2011.
 234. Grover TR , Asikainen TM , Kinsella JP , Abman SH , White CW . Hypoxia‐inducible factors HIF‐1α and HIF‐2α are decreased in an experimental model of severe respiratory distress syndrome in preterm lambs. Am J Physiol Lung Cell Mol Physiol 292: L1345‐L1351, 2007.
 235. Groves BM , Droma T , Sutton JR , McCullough RG , McCullough RE , Zhuang J , Rapmund G , Sun S , Janes C , Moore LG . Minimal hypoxic pulmonary hypertension in normal Tibetans at 3,658 m. J Appl Physiol 74: 312‐318, 1993.
 236. Grzenda A , Shannon J , Fisher J , Arkovitz MS . Timing and expression of the angiopoietin‐1‐Tie‐2 pathway in murine lung development and congenital diaphragmatic hernia. Dis Mod Mech 6: 106‐114, 2013.
 237. Guembe L , Villaro AC . Histochemical demonstration of neuronal nitric oxide synthase during development of mouse respiratory tract. Am J Respir Cell Mol Biol 20: 342‐351, 1999.
 238. Guerin C , Badet M , Rosselli S , Heyer L , Sab JM , Langevin B , Philit F , Fournier G , Robert D . Effects of prone position on alveolar recruitment and oxygenation in acute lung injury. Intensive Care Med 25: 1222‐1230, 1999.
 239. Guilluy C , Sauzeau V , Rolli‐Derkinderen M , Guerin P , Sagan C , Pacaud P , Loirand G . Inhibition of RhoA/Rho kinase pathway is involved in the beneficial effect of sildenafil on pulmonary hypertension. Br J Pharmacol 146: 1010‐1018, 2005.
 240. Gulino‐Debrac DCP . Mechanotransduction at the basis of endothelial barrier function. Tissue Barriers 1: e24180, 2013.
 241. Gumusel B , Orhan D , Tolunay O , Uma S . The role of nitric oxide in mediating nonadrenergic, noncholinergic relaxation in rat pulmonary artery. Nitric Oxide 5: 296‐301, 2001.
 242. Gupta ML , Rao KS , Anand IS , Banerjee AK , Boparai MS . Lack of smooth muscle in the small pulmonary arteries of the native Ladakhi. Is the Himalayan highlander adapted? Am Rev Resp Dis 145:1201‐1204, 1992.
 243. Haberberger R , Schemann M , Sann H , Kummer W . Innervation pattern of guinea pig pulmonary vasculature depends on vascular diameter. J Appl Physiol 82: 426‐434, 1997.
 244. Hakim TS , Dean GW , Lisbona R . Effect of body posture on spatial distribution of pulmonary blood flow. J Appl Physiol 64: 1160‐1170, 1988.
 245. Hakim TS , Lisbona R , Dean GW . Effect of cardiac output on gravity‐dependent and nondependent inequality in pulmonary blood flow. J Appl Physiol 66: 1570‐1578, 1989.
 246. Hales CA , Rouse ET , Kazemi H . Failure of saralasin acetate, a competitive inhibitor of angiotensin II, to diminish alveolar hypoxic vasoconstriction in the dog. Cardiovasc Res 11: 541‐546, 1977.
 247. Hall SM , Hislop AA , Haworth SG . Origin, differentiation, and maturation of human pulmonary veins. Am J Resp Cell Mol Biol 26: 333‐340, 2002.
 248. Hall SM , Hislop AA , Pierce CM , Haworth SG . Prenatal origins of human intrapulmonary arteries: Formation and smooth muscle maturation. Am J Resp Cell Mol Biol 23: 194‐203, 2000.
 249. Hasunuma K , Yamaguchi T , Rodman DM , O'Brien RF , McMurtry IF . Effects of inhibitors of EDRF and EDHF on vasoreactivity of perfused rat lungs. Am J Physiol Lung Cell Mol Physiol 260: L97‐L104, 1991.
 250. Hauge A , Lunde PK , Waaler BA . The effect of bradykinin, kallidin and eledoisin upon the pulmonary vascular bed of an isolated blood‐perfused rabbit lung preparation. Acta Physiol Scan 66: 269‐277, 1966.
 251. Haynes J, Jr. , Obiako B , Thompson WJ , Downey J . Adenosine‐induced vasodilation: Receptor characterization in pulmonary circulation. Am J Physiol Heart Circ Physiol 268: H1862‐H1868, 1995.
 252. Haywood GA , Sneddon JF , Bashir Y , Jennison SH , Gray HH , McKenna WJ . Adenosine infusion for the reversal of pulmonary vasoconstriction in biventricular failure. A good test but a poor therapy. Circulation 86: 896‐902, 1992.
 253. Heath D , Smith P , Rios Dalenz J , Williams D , Harris P . Small pulmonary arteries in some natives of La Paz, Bolivia. Thorax 36: 599‐604, 1981.
 254. Hedenstierna G , White FC , Wagner PDC . Spatial distribution of pulmonary blood flow in the dog with PEEP ventilation. J Appl Physiol 47:938‐946, 1979.
 255. Heinonen I , Savolainen AM , Han C , Kemppainen J , Oikonen V , Luotolahti M , Duncker DJ , Merkus D , Knuuti J , Kalliokoski KK . Pulmonary blood flow and its distribution in highly trained endurance athletes and healthy control subjects. J Appl Physiol 114: 329‐334, 2013.
 256. Henderson AC , Sa RC , Theilmann RJ , Buxton RB , Prisk GK , Hopkins SRCP . The gravitational distribution of ventilation‐perfusion ratio is more uniform in prone than supine posture in the normal human lung. J Appl Physiol 115: 313‐324, 2013.
 257. Heymann MA . Control of the pulmonary circulation in the fetus and during the transitional period to air breathing. Eur J Ob Gyn Repro Biol 84: 127‐132, 1999.
 258. Higenbottam T , Marriott H , Cremona G , Laude E , Bee D . The acute effects of dexfenfluramine on human and porcine pulmonary vascular tone and resistance. Chest 116: 921‐930, 1999.
 259. Hirenallur SD , Haworth ST , Leming JT , Chang J , Hernandez G , Gordon JB , Rusch NJ . Upregulation of vascular calcium channels in neonatal piglets with hypoxia‐induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 295: L915‐L924, 2008.
 260. Hisatsune C , Kuroda Y , Nakamura K , Inoue T , Nakamura T , Michikawa T , Mizutani A , Mikoshiba K . Regulation of TRPC6 channel activity by tyrosine phosphorylation. J Biol Chem 279: 18887, 2004.
 261. Hislop A , Reid L . Intra‐pulmonary arterial development during fetal life‐branching pattern and structure. J Anat 113: 35‐48, 1972.
 262. Hislop A , Reid L . Fetal and childhood development of the intrapulmonary veins in man–branching pattern and structure. Thorax 28: 313‐319, 1973.
 263. Hislop A , Reid L . New findings in pulmonary arteries of rats with hypoxia‐induced pulmonary hypertension. Br J Exp Pathol 57: 542‐554, 1976.
 264. Hislop A , Reid L . Normal structure and dimensions of the pulmonary arteries in the rat. J Anat 125: 71‐83, 1978.
 265. Hislop AA , Pierce CM . Growth of the vascular tree. Paediat Resp Rev 1: 321‐327, 2000.
 266. Hoffmann J , Yin J , Kukucka M , Yin N , Saarikko I , Sterner‐Kock A , Fujii H , Leong‐Poi H , Kuppe H , Schermuly RT , Kuebler WM . Mast cells promote lung vascular remodelling in pulmonary hypertension. Eur Respir J 37: 1400‐1410, 2011.
 267. Hogan J , Smith P , Heath D , Harris P . The thickness of the alveolar capillary wall in the human lung at high and low altitude. Br J Dis Chest 80: 13‐18, 1986.
 268. Holm P . Endothelin in the pulmonary circulation with special reference to hypoxic pulmonary vasoconstriction. Scand Cardiovas J Supplement 46: 1‐40, 1997.
 269. Hong J , Kandasamy K , Marimuthu M , Choi CS , Kim S . Electrical cell‐substrate impedance sensing as a non‐invasive tool for cancer cell study. Analyst 136: 237‐245, 2011.
 270. Hood S , Birnie D , Nasser A , Hillis WS . Effect of ketanserin on central haemodynamics and coronary circulation. J Cardiovasc Pharmacol 32: 983‐987, 1998.
 271. Howell K , Preston RJ , McLoughlin P . Chronic hypoxia causes angiogenesis in addition to remodelling in the adult rat pulmonary circulation. J Physiol 547: 133‐145, 2003.
 272. Hu G , Minshall RD . Regulation of transendothelial permeability by Src kinase. Microvasc Res 77: 21‐25, 2009.
 273. Hu G , Place AT , Minshall RD . Regulation of endothelial permeability by Src kinase signaling: Vascular leakage versus transcellular transport of drugs and macromolecules. Chem Biol Interact 171: 177‐189, 2008.
 274. Hu H , Sung A , Zhao G , Shi L , Qiu D , Nishimura T , Kao PN . Simvastatin enhances bone morphogenetic protein receptor type II expression. Biochem Biophys Res Commun 339: 59‐64, 2006.
 275. Hu SL , He HL , Pan C , Liu AR , Liu SQ , Liu L , Huang YZ , Guo FM , Yang Y , Qiu HBC . The effect of prone positioning on mortality in patients with acute respiratory distress syndrome: a meta‐analysis of randomized controlled trials. Crit Care 18: R109, 2014.
 276. Hubloue I , Rondelet B , Kerbaul F , Biarent D , Milani GM , Staroukine M , Bergmann P , Naeije R , Leeman M . Endogenous angiotensin II in the regulation of hypoxic pulmonary vasoconstriction in anaesthetized dogs. Crit Care 8: R163‐R171, 2004.
 277. Hughes M , West JB . Last word on Point:Counterpoint: Gravity is/is not the major factor determining the distribution of blood flow in the human lung. J Appl Physiol 104: 1539, 2008.
 278. Hughes M , West JB . Point: Gravity is the major factor determining the distribution of blood flow in the human lung. J Appl Physiol 104: 1531‐1533, 2008.
 279. Huh D , Matthews BD , Mammoto A , Montoya‐Zavala M , Hsin HY , Ingber DEC . Reconstituting organ‐level lung functions on a chip. Science 328: 1662‐1668, 2010.
 280. Huhta JC , Cohen M , Gutgesell HP . Patency of the ductus arteriosus in normal neonates: Two‐dimensional echocardiography versus Doppler assessment. J Am Col Cardiol 4: 561‐564, 1984.
 281. Hunter CJ , Dejam A , Blood AB , Shields H , Kim‐Shapiro DB , Machado RF , Tarekegn S , Mulla N , Hopper AO , Schechter AN , Power GG , Gladwin MT . Inhaled nebulized nitrite is a hypoxia‐sensitive NO‐dependent selective pulmonary vasodilator. Nat Med 10: 1122‐1127, 2004.
 282. Hyman AL , Kadowitz PJ . Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat. Circ Res 45: 404‐409, 1979.
 283. Hyman AL , Lippton HL , Kadowitz PJ . Autonomic regulation of the pulmonary circulation. J Cardiovasc Pharmacol 7(Suppl 3): S80‐S95, 1985.
 284. Hyman AL , Lippton HL , Kadowitz PJ . Analysis of pulmonary vascular responses in cats to sympathetic nerve stimulation under elevated tone conditions. Evidence that neuronally released norepinephrine acts on alpha 1‐, alpha 2‐, and beta 2‐adrenoceptors. Circ Res 67: 862‐870, 1990.
 285. Hyman AL , Nandiwada P , Knight DS , Kadowitz PJ . Pulmonary vasodilator responses to catecholamines and sympathetic nerve stimulation in the cat. Evidence that vascular beta‐2 adrenoreceptors are innervated. Circ Res 48: 407‐415, 1981.
 286. Hyvelin J‐M , Howell K , Nichol A , Costello CM , Preston RJ , McLoughlin P . Inhibition of Rho‐kinase attenuates hypoxia‐induced angiogenesis in the pulmonary circulation. Circ Res 97: 185‐191, 2005.
 287. Ignarro LJ , Byrns RE , Buga GM , Wood KS . Mechanisms of endothelium‐dependent vascular smooth muscle relaxation elicited by bradykinin and VIP. Am J Physiol 253: H1074‐H1082, 1987.
 288. Ignarro LJ , Lippton H , Edwards JC , Baricos WH , Hyman AL , Kadowitz PJ , Gruetter CA . Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: Evidence for the involvement of S‐nitrosothiols as active intermediates. J Pharmacol Exp Ther 218: 739‐749, 1981.
 289. Ikeda T , Takahashi H , Suzuki A , Ueno N , Yokose S , Yamaguchi A , Yoshiki S . Cloning of rat type I receptor cDNA for bone morphogenetic protein‐2 and bone morphogenetic protein‐4, and the localization compared with that of the ligands. Dev Dynam 206: 318‐329, 1996.
 290. International PPHC, Lane KB , Machado RD , Pauciulo MW , Thomson JR , Phillips JA, III , Loyd JE , Nichols WC , Trembath RC . Heterozygous germline mutations in BMPR2, encoding a TGF‐beta receptor, cause familial primary pulmonary hypertension. Nat Gen 26: 81‐84, 2000.
 291. Ishikura K , Yamada N , Ito M , Ota S , Nakamura M , Isaka N , Nakano T . Beneficial acute effects of rho‐kinase inhibitor in patients with pulmonary arterial hypertension. Circ J 70: 174‐178, 2006.
 292. Ivy DD , Abman SH , Barst RJ , Berger RM , Bonnet D , Fleming TR , Haworth SG , Raj JU , Rosenzweig EB , Schulze Neick I , Steinhorn RH , Beghetti M . Pediatric pulmonary hypertension. J Am Col Cardiol 62: D117‐D126, 2013.
 293. Ivy DD , Kinsella JP , Abman SH . Endothelin blockade augments pulmonary vasodilation in the ovine fetus. J Appl Physiol 81: 2481‐2487, 1996.
 294. Iwata K , Doi A , Ohji G , Oka H , Oba Y , Takimoto K , Igarashi W , Gremillion DH , Shimada T . Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): A systematic review and meta‐analysis. Intern Med 49: 2423‐2432, 2010.
 295. Iyer NV , Kotch LE , Agani F , Leung SW , Laughner E , Wenger RH , Gassmann M , Gearhart JD , Lawler AM , Yu AY , Semenza GL . Cellular and developmental control of O2 homeostasis by hypoxia‐inducible factor 1α. Genes Dev 12: 149‐162, 1998.
 296. Jacobs ER , Zeldin DC . The lung HETEs (and EETs) up. Am J Physiol Heart Circ Physiol 280: H1‐H10, 2001.
 297. Jameson AG . Diffusion of gases from alveolus to precapillary arteries. Science 139: 826‐828, 1963.
 298. Jansen TL , Morice AH , Brown MJ . A comparison of the vasodilator responses to atrial peptides in the pulmonary and renal arteries of the pig in vitro. Br J Pharmacol 91: 687‐691, 1987.
 299. Janssen LJ , Premji M , Netherton S , Coruzzi J , Lu‐Chao H , Cox PG . Vasoconstrictor actions of isoprostanes via tyrosine kinase and Rho kinase in human and canine pulmonary vascular smooth muscles. Br J Pharmacol 132: 127‐134, 2001.
 300. Jernigan NL , Walker BR , Resta TC . Reactive oxygen species mediate RhoA/Rho kinase‐induced Ca2+ sensitization in pulmonary vascular smooth muscle following chronic hypoxia. Am J Physiol Lung Cell Mol Physiol 295: L515‐L529, 2008.
 301. Jiang X , Malkovskiy AV , Tian W , Sung YK , Sun W , Hsu JL , Manickam S , Wagh D , Joubert LM , Semenza GL , Rajadas J , Nicolls MR . Promotion of airway anastomotic microvascular regeneration and alleviation of airway ischemia by deferoxamine nanoparticles. Biomaterials 35: 803‐813, 2014.
 302. Jin HK , Yang RH , Thornton RM , Chen YF , Jackson R , Oparil S . Atrial natriuretic peptide lowers pulmonary arterial pressure in hypoxia‐adapted rats. J Appl Physiol 65: 1729‐1735, 1988.
 303. Jin Y , Lee SJ , Minshall RD , Choi AM . Caveolin‐1: A critical regulator of lung injury. Am J Physiol Lung Cell Mol Physiol 300: L151, 2011.
 304. Johnson DE , Georgieff MK . Pulmonary neuroendocrine cells. Their secretory products and their potential roles in health and chronic lung disease in infancy. Am Rev Respir Dis 140: 1807‐1812, 1989.
 305. Johnson P , Maxwell DJ , Tynan MJ , Allan LD . Intracardiac pressures in the human fetus. Heart 84: 59‐63, 2000.
 306. Jones AT , Hansell DM , Evans TWC . Pulmonary perfusion in supine and prone positions: An electron‐beam computed tomography study. J Appl Physiol 90: 1342‐1348, 2001.
 307. Kadowitz PJ , Chapnick BM , Joiner PD , Hyman AL . Influence of inhibitors of prostaglandin synthesis on the canine pulmonary vascular bed. Am J Physiol 229: 941‐946, 1975.
 308. Kadowitz PJ , Hyman AL . Effect of sympathetic nerve stimulation on pulmonary vascular resistance in the dog. Circ Res 32: 221‐227, 1973.
 309. Kadowitz PJ , Knight DS , Hibbs RG , Ellison JP , Joiner PD , Brody MJ , Hyman AL . Influence of 5‐ and 6‐hydroxydopamine on adrenergic transmission and nerve terminal morphology in the canine pulmonary vascular bed. Circ Res 39: 191‐199, 1976.
 310. Kalinichenko VV , Lim L , Stolz DB , Shin B , Rausa FM , Clark J , Whitsett JA , Watkins SC , Costa RH . Defects in pulmonary vasculature and perinatal lung hemorrhage in mice heterozygous null for the Forkhead Box f1 transcription factor. Dev Biol 235: 489‐506, 2001.
 311. Kamler M , Nowak K , Bock M , Herold U , Motsch J , Hagl S , Gebhard MM , Jakob H . Bronchial artery revascularization restores peribronchial tissue oxygenation after lung transplantation. J Heart Lung Trans 23: 763‐766, 2004.
 312. Kane DW , Tesauro T , Koizumi T , Gupta R , Newman JH . Exercise‐induced pulmonary vasoconstriction during combined blockade of nitric oxide synthase and beta adrenergic receptors. J Clin Invest 93: 677‐683, 1994.
 313. Kasai T , Chiba S . Macroscopic anatomy of the bronchial arteries. Anatomischer Anzeiger 145: 166‐181, 1979.
 314. Katsiki N , Wierzbicki AS , Mikhailidis DP . Pulmonary arterial hypertension and statins: An update. Cur Opin Cardiol 26: 322‐326, 2011.
 315. Kawkitinarong K , Linz‐McGillem L , Birukov KG , Garcia JG . Differential regulation of human lung epithelial and endothelial barrier function by thrombin. Am J Respir Cell Mol Biol 31: 517‐527, 2004.
 316. Kawut SM , Bagiella E , Lederer DJ , Shimbo D , Horn EM , Roberts KE , Hill NS , Barr RG , Rosenzweig EB , Post W , Tracy RP , Palevsky HI , Hassoun PM , Girgis RE , Group A‐SS . Randomized clinical trial of aspirin and simvastatin for pulmonary arterial hypertension: ASA‐STAT. Circulation 123: 2985‐2993, 2011.
 317. Kay JM , Harris P , Heath D . Pulmonary hypertension produced in rats by ingestion of Crotalaria spectabilis seeds. Thorax 22: 176‐179, 1967.
 318. Kelly L , Kolbe J , Mitzner W , Spannhake EW , Bromberger‐Barnea B , Menkes H . Bronchial blood flow affects recovery from constriction in dog lung periphery. J Appl Physiol 60: 1954‐1959, 1986.
 319. Kern DF , Malik AB . Microvascular albumin permeability in isolated perfused lung: Effects of EDTA. J Appl Physiol 58: 372‐375, 1985.
 320. Keseru B , Barbosa‐Sicard E , Popp R , Fisslthaler B , Dietrich A , Gudermann T , Hammock BD , Falck JR , Weissmann N , Busse R , Fleming I . Epoxyeicosatrienoic acids and the soluble epoxide hydrolase are determinants of pulmonary artery pressure and the acute hypoxic pulmonary vasoconstrictor response. FASEB J 22: 4306‐4315, 2008.
 321. Kevil CG , Payne DK , Mire E , Alexander JS . Vascular permeability factor/vascular endothelial cell growth factor‐mediated permeability occurs through disorganization of endothelial junctional proteins. J Biol Chem 273: 15099‐15103, 1998.
 322. Khalpey Z , Gilfeather MS , Camp PC, Jr. , Jaklitsch MT . Controlled antegrade single lung reperfusion during double lung transplant. In Cardiovas Thor Surg 9: 932‐933, 2009.
 323. Kiely DG , Cargill RI , Lipworth BJ . Angiotensin II receptor blockade and effects on pulmonary hemodynamics and hypoxic pulmonary vasoconstriction in humans. Chest 110: 698‐703, 1996.
 324. Kimura H , Mittal CK , Murad F . Activation of guanylate cyclase from rat liver and other tissues by sodium azide. J Biol Chem 250: 8016‐8022, 1975.
 325. Kiserud T . Physiology of the fetal circulation. Sem Fetal Neonat Med 10: 493‐503, 2005.
 326. Kizub IV , Strielkov IV , Shaifta Y , Becker S , Prieto‐Lloret J , Snetkov VA , Soloviev AI , Aaronson PI , Ward JP . Gap junctions support the sustained phase of hypoxic pulmonary vasoconstriction by facilitating calcium sensitization. Cardiovas Res 99: 404‐411, 2013.
 327. Komarova Y , Malik AB . Regulation of endothelial permeability via paracellular and transcellular transport pathways. Ann Rev Physiol 72: 463‐493, 2010.
 328. Komori K , Lorenz RR , Vanhoutte PM . Nitric oxide, ACh, and electrical and mechanical properties of canine arterial smooth muscle. Am J Physiol 255: H207‐H212, 1988.
 329. Konduri GG , Mital S , Gervasio CT , Rotta AT , Forman K . Purine nucleotides contribute to pulmonary vasodilation caused by birth‐related stimuli in the ovine fetus. Am J Physiol 272: H2377‐H2384, 1997.
 330. Konduri GG , Woodard LL , Mukhopadhyay A , Deshmukh DR . Adenosine is a pulmonary vasodilator in newborn lambs. Am Rev Respir Dis 146: 670‐676, 1992.
 331. Kotch LE , Iyer NV , Laughner E , Semenza GL . Defective vascularization of HIF‐1a‐null embryos is not associated with VEGF deficiency but with mesenchymal cell death. Dev Biol 209: 254‐267, 1999.
 332. Kotecha S . Lung growth for beginners. Paediat Resp Rev 1: 308‐313, 2000.
 333. Kowalski TF , Guidotti S , Deffebach M , Kubilis P , Bishop M . Bronchial circulation in pulmonary artery occlusion and reperfusion. J Appl Physiol 68: 125‐129, 1990.
 334. Kramer GC , Lindsey DC , Wu CH , Mertens S , Russell LA , Cross CE . Airway blood flow distribution and lung edema after histamine infusion in awake sheep. J Appl Physiol 65: 1847‐1854, 1988.
 335. Krebs MO , Boemke W , Simon S , Wenz M , Kaczmarczyk G . Acute hypoxic pulmonary vasoconstriction in conscious dogs decreases renin and is unaffected by losartan. J Appl Physiol 86: 1914‐1919, 1999.
 336. Kuhr FK , Smith KA , Song MY , Levitan I , Yuan JX‐J . New mechanisms of pulmonary arterial hypertension: role of Ca2+ signaling. Am J Physiol Heart Circ Physiol 302: H1546‐H1562, 2012.
 337. Kummer W . Pulmonary vascular innervation and its role in responses to hypoxia: Size matters! Proc Am Thorac Soc 8: 471‐476, 2011.
 338. Kummer W , Fischer A , Kurkowski R , Heym C . The sensory and sympathetic innervation of guinea‐pig lung and trachea as studied by retrograde neuronal tracing and double‐labelling immunohistochemistry. Neuroscience 49: 715‐737, 1992.
 339. Kunichika N , Landsberg JW , Yu Y , Kunichika H , Thistlethwaite PA , Rubin LJ , Yuan JX . Bosentan inhibits transient receptor potential channel expression in pulmonary vascular myocytes. Am J Respir Crit Care Med 170: 1101‐1107, 2004.
 340. Lai‐Fook SJ . A continuum mechanics analysis of pulmonary vascular interdependence in isolated dog lobes. J Appl Physiol 46: 419‐429, 1979.
 341. Lamm WJ , Graham MM , Albert RK . Mechanism by which the prone position improves oxygenation in acute lung injury. Am J Respir Crit Care Med 150: 184‐193, 1994.
 342. Landsberg JW , Yuan JX . Calcium and TRP channels in pulmonary vascular smooth muscle cell proliferation. News Physiol Sci 19: 44‐50, 2004.
 343. Larkin EK , Newman JH , Austin ED , Hemnes AR , Wheeler L , Robbins IM , West JD , Phillips JA, III , Hamid R , Loyd JE . Longitudinal analysis casts doubt on the presence of genetic anticipation in heritable pulmonary arterial hypertension. Am J Respir Crit Care Med 186: 892‐896, 2012.
 344. Larsson J , Goumans MJ , Sjostrand LJ , van Rooijen MA , Ward D , Leveen P , Xu X , ten Dijke P , Mummery CL , Karlsson S . Abnormal angiogenesis but intact hematopoietic potential in TGF‐beta type I receptor‐deficient mice. EMBO J 20: 1663‐1673, 2001.
 345. Lauer T , Preik M , Rassaf T , Strauer BE , Deussen A , Feelisch M , Kelm M . Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Nat Acad Sci U S A 98: 12814‐12819, 2001.
 346. Lauweryns JM , de Bock V , Guelinckx P , Decramer M . Effects of unilateral hypoxia on neuroepithelial bodies in rabbit lungs. J Appl Physiol 55: 1665‐1668, 1983.
 347. Leach RM , Hill HM , Snetkov VA , Robertson TP , Ward JP . Divergent roles of glycolysis and the mitochondrial electron transport chain in hypoxic pulmonary vasoconstriction of the rat: identity of the hypoxic sensor. J Appl Physiol 536: 211‐224, 2001.
 348. Leggett K , Maylor J , Undem C , Lai N , Lu W , Schweitzer KS , King LS , Myers AC , Sylvester JT , Sidhaye VK , Shimoda LA . Hypoxia‐induced migration in pulmonary arterial smooth muscle cells requires calcium‐dependent upregulation of aquaporin 1. Am J Physiol Lung Cell Mol Physiol 303: L343‐L353, 2012.
 349. Lejeune P , Vachiery JL , Leeman M , Brimioulle S , Hallemans R , Melot C , Naeije R . Absence of parasympathetic control of pulmonary vascular pressure‐flow plots in hyperoxic and hypoxic dogs. Respir Physiol 78: 123‐133, 1989.
 350. Levine BW , Talamo RC , Kazemi H . Action and metabolism of bradykinin in dog lung. J Appl Physiol 34: 821‐826, 1973.
 351. Lewis AB , Heymann MA , Rudolph AM . Gestational changes in pulmonary vascular responses in fetal lambs in utero. Circ Res 39: 536‐541, 1976.
 352. Li VS , Ng SS , Boersema PJ , Low TY , Karthaus WR , Gerlach JP , Mohammed S , Heck AJ , Maurice MM , Mahmoudi T , Clevers H . Wnt signaling through inhibition of beta‐catenin degradation in an intact Axin1 complex. Cell 149: 1245‐1256, 2012.
 353. Liebow AA . Patterns of origin and distribution of the major bronchial arteries in man. Am J Anat 117: 19‐32, 1965.
 354. Lim LH , Bochner BS , Wagner EM . Leukocyte recruitment in the airways: An intravital microscopic study of rat tracheal microcirculation. Am J Physiol Lung Cell Mol Physiol 282: L959‐L967, 2002.
 355. Lin MJ , Leung GP , Zhang WM , Yang XR , Yip KP , Tse CM , Sham JS . Chronic hypoxia‐induced upregulation of store‐operated and receptor‐operated Ca2+ channels in pulmonary arterial smooth muscle cells: A novel mechanism of hypoxic pulmonary hypertension. Circ Res 95: 496‐505, 2004.
 356. Lindberg F , Andersson KE . Vasodilator responses to alpha‐human‐atrial natriuretic peptide in isolated omental and pulmonary arteries from rabbit and man. Acta Physiol Scand 134: 391‐397, 1988.
 357. Linehan JH , Haworth ST , Nelin LD , Krenz GS , Dawson CA . A simple distensible vessel model for interpreting pulmonary vascular pressure‐flow curves. J Appl Physiol 73: 987‐994, 1992.
 358. Link DP , Parsons GH , Lantz BM , Gunther RA , Green JF , Cross CE . Measurement of bronchial blood flow in the sheep by video dilution technique. Thorax 40: 143‐149, 1985.
 359. Lippton HL , Nandiwada PA , Hyman AL , Kadowitz PJ . Influence of cyclooxygenase blockade on responses to isoproterenol, bradykinin and nitroglycerin in the feline pulmonary vascular bed. Prostaglandins 28: 253‐270, 1984.
 360. Liu F , Wu JY , Beasley D , Orr JA . TxA2‐induced pulmonary artery contraction requires extracellular calcium. Respir Physiol 109: 155‐166, 1997.
 361. Liu JQ , Sham JS , Shimoda LA , Kuppusamy P , Sylvester JT . Hypoxic constriction and reactive oxygen species in porcine distal pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 285: L322‐L333, 2003.
 362. Liu SF , Crawley DE , Evans TW , Barnes PJ . Endothelium‐dependent nonadrenergic, noncholinergic neural relaxation in guinea pig pulmonary artery. J Pharmacol Exp Ther 260: 541‐548, 1992.
 363. Liu SF , Crawley DE , Rohde JA , Evans TW , Barnes PJ . Role of nitric oxide and guanosine 3',5'‐cyclic monophosphate in mediating nonadrenergic, noncholinergic relaxation in guinea‐pig pulmonary arteries. Br J Pharmacol 107: 861‐866, 1992.
 364. Liu SF , McCormack DG , Evans TW , Barnes PJ . Evidence for two P2‐purinoceptor subtypes in human small pulmonary arteries. Br J Pharmacol 98: 1014‐1020, 1989.
 365. Liu XR , Zhang MF , Yang N , Liu Q , Wang RX , Cao YN , Yang XR , Sham JS , Lin MJ . Enhanced store‐operated Ca2+ entry and TRPC channel expression in pulmonary arteries of monocrotaline‐induced pulmonary hypertensive rats. Am J Physiol Cell Physiol 302: C77‐C87, 2012.
 366. Liu Y , Suzuki YJ , Day RM , Fanburg BL . Rho kinase‐induced nuclear translocation of ERK1/ERK2 in smooth muscle cell mitogenesis caused by serotonin. Circ Res 95: 579‐586, 2004.
 367. Lloyd TC . Effect of alveolar hypoxia on pulmonary vascular resistance. J Appl Physiol 19: 1086‐1094, 1964.
 368. Lloyd TC, Jr . Role of nerve pathways in the hypoxic vasoconstriction of lung. J Appl Physiol 21: 1351‐1355, 1966.
 369. Long L , Ormiston ML , Yang X , Southwood M , Graf S , Machado RD , Mueller M , Kinzel B , Yung LM , Wilkinson JM , Moore SD , Drake KM , Aldred MA , Yu PB , Upton PD , Morrell NW . Selective enhancement of endothelial BMPR‐II with BMP9 reverses pulmonary arterial hypertension. Nature Med 21: 777‐785, 2015.
 370. Long WM , Sprung CL , el Fawal H , Yerger LD , Eyre P , Abraham WM , Wanner A . Effects of histamine on bronchial artery blood flow and bronchomotor tone. J Appl Physiol 59: 254‐261, 1985.
 371. Lopez‐Muniz R , Stephens NL , Bromberger‐Barnea B , Permutt S , Riley RLC . Critical closure of pulmonary vessels analyzed in terms of Starling resistor model. J Appl Physiol 24: 625‐635, 1968.
 372. Losapio JL , Sprague RS , Lonigro AJ , Stephenson AH . 5,6‐EET‐induced contraction of intralobar pulmonary arteries depends on the activation of Rho‐kinase. J Appl Physiol 99: 1391‐1396, 2005.
 373. Loughna S , Sato TN . Angiopoietin and Tie signaling pathways in vascular development. Matrix Biol 20: 319‐325, 2001.
 374. Loukas M , Hanna M , Chen J , Tubbs RS , Anderson RH . Extracardiac coronary arterial anastomoses. Clin Anat 24: 137‐142, 2011.
 375. Low FN . Electron microscopy of the rat lung. Anat Rec 113: 437‐449, 1952.
 376. Lowe K , Alvarez D , King J , Stevens T . Phenotypic heterogeneity in lung capillary and extra‐alveolar endothelial cells. Increased extra‐alveolar endothelial permeability is sufficient to decrease compliance. J Surg Res 143: 70‐77, 2007.
 377. Lowery JW , de Caestecker MP . BMP signaling in vascular development and disease. Cytokine Growth Factor Rev 21: 287‐298, 2010.
 378. Lu W , Ran P , Zhang D , Lai N , Zhong N , Wang J . Bone morphogenetic protein 4 enhances canonical transient receptor potential expression, store‐operated Ca2+ entry, and basal [Ca2+]i in rat distal pulmonary arterial smooth muscle cells. Am J Physiol Cell Physiol 299: C1370‐C1378, 2010.
 379. Lu X , Bijli KM , Ramirez A , Murphy TC , Kleinhenz J , Hart CM . Hypoxia downregulates PPARgamma via an ERK1/2‐NF‐kappaB‐Nox4‐dependent mechanism in human pulmonary artery smooth muscle cells. Free Radic Biol Med 63: 151‐160, 2013.
 380. Luckraz H , Goddard M , McNeil K , Atkinson C , Charman SC , Stewart S , Wallwork J . Microvascular changes in small airways predispose to obliterative bronchiolitis after lung transplantation. J Heart Lung Trans 23: 527‐531, 2004.
 381. Luecke T , Pelosi PCP . Clinical review: Positive end‐expiratory pressure and cardiac output. Crit Care 9: 607‐621, 2005.
 382. Luke T , Maylor J , Undem C , Sylvester JT , Shimoda LA . Kinase dependent activation of voltage‐gated Ca2+ channels by ET‐1 in pulmonary arterial myocytes during chronic hypoxia. Am J Physiol Lung Cell Mol Physiol 302: L1128‐L1139, 2012.
 383. Lundgrin EL , Park MM , Sharp J , Tang WH , Thomas JD , Asosingh K , Comhair SA , DiFilippo FP , Neumann DR , Davis L , Graham BB , Tuder RM , Dostanic I , Erzurum SC . Fasting 2‐deoxy‐2‐[18F]fluoro‐D‐glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year. Ann Am Thorac Soc 10: 1‐9, 2013.
 384. Ma L , Chung WK . The genetic basis of pulmonary arterial hypertension. Human Gen 133: 471‐479, 2014.
 385. Machado RD , Pauciulo MW , Thomson JR , Lane KB , Morgan NV , Wheeler L , Phillips JA, III , Newman J , Williams D , Galie N , Manes A , McNeil K , Yacoub M , Mikhail G , Rogers P , Corris P , Humbert M , Donnai D , Martensson G , Tranebjaerg L , Loyd JE , Trembath RC , Nichols WC . BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Human Gen 68: 92‐102, 2001.
 386. MacIntyre PD , Bhargava B , Hogg KJ , Gemmill JD , Hillis WS . Effect of subcutaneous sumatriptan, a selective 5HT1 agonist, on the systemic, pulmonary, and coronary circulation. Circulation 87: 401‐405, 1993.
 387. MacLean MR , Alexander D , Stirrat A , Gallagher M , Douglas SA , Ohlstein EH , Morecroft I , Polland K . Contractile responses to human urotensin‐II in rat and human pulmonary arteries: Effect of endothelial factors and chronic hypoxia in the rat. Br J Pharmacol 130: 201‐204, 2000.
 388. MacLean MR , Clayton RA , Hillis SW , McIntyre PD , Peacock AJ , Templeton AG . 5‐HT1‐receptor‐mediated vasoconstriction in bovine isolated pulmonary arteries: influences of vascular endothelium and tone. Pulm Pharmacol 7: 65‐72, 1994.
 389. MacLean MR , Clayton RA , Templeton AG , Morecroft I . Evidence for 5‐HT1‐like receptor‐mediated vasoconstriction in human pulmonary artery. Br J Pharmacol 119: 277‐282, 1996.
 390. Maclean MR , Dempsie Y . The serotonin hypothesis of pulmonary hypertension revisited. Adv Exp Med Biol 661: 309‐322, 2010.
 391. Madden JA , Ray DE , Keller PA , Kleinman JG . Ion exchange activity in pulmonary artery smooth muscle cells: the response to hypoxia. Am J Physiol Lung Cell Mol Physiol 280: L264‐L271, 2001.
 392. Maeda Y , Dave V , Whitsett JA . Transcriptional control of lung morphogenesis. Physiol Rev 87: 219‐244, 2007.
 393. Magno MG , Fishman AP . Origin, distribution, and blood flow of bronchial circulation in anesthetized sheep. J Appl Physiol 53: 272‐279, 1982.
 394. Mahapatra S , Nishimura RA , Sorajja P , Cha S , McGoon MD . Relationship of pulmonary arterial capacitance and mortality in idiopathic pulmonary arterial hypertension. J Am Col Cardiol 21:799‐803, 2006.
 395. Mahlapuu M , Enerback S , Carlsson P . Haploinsufficiency of the forkhead gene Foxf1, a target for sonic hedgehog signaling, causes lung and foregut malformations. Development 128: 2397‐2406, 2001.
 396. Mahlapuu M , Ormestad M , Enerback S , Carlsson P . The forkhead transcription factor Foxf1 is required for differentiation of extra‐embryonic and lateral plate mesoderm. Development 128: 155‐166, 2001.
 397. Mair KM , MacLean MR , Morecroft I , Dempsie Y , Palmer TM . Novel interactions between the 5‐HT transporter, 5‐HT1B receptors and Rho kinase in vivo and in pulmonary fibroblasts. Br J Pharmacol 155:606‐616, 2008.
 398. Malik AB , Mewmark JM . Adrenergic mechanisms and the pulmonary vascular response to respiratory acidosis. Respiration 33: 179‐187, 1976.
 399. Maltepe E , Schmidt JV , Baunoch D , Bradfield CA , Simon MC . Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nat 386: 403‐407, 1997.
 400. Marsboom G , Toth PT , Ryan JJ , Hong Z , Wu X , Fang YH , Thenappan T , Piao L , Zhang HJ , Pogoriler J , Chen Y , Morrow E , Weir EK , Rehman J , Archer SL . Dynamin‐related protein 1‐mediated mitochondrial mitotic fission permits hyperproliferation of vascular smooth muscle cells and offers a novel therapeutic target in pulmonary hypertension. Circ Res 110: 1484‐1497, 2012.
 401. Martin GS , Brigham KL . Fluid flux and clearance in acute lung injury. Compr Physiol 2: 2471‐2480, 2012.
 402. Matran R , Alving K , Hemsen A , Lundberg JM . Endothelin‐1 increases airway mucosa blood flow in the pig. Agents Actions 31: 237‐241, 1990.
 403. McCormack DG , Clarke B , Barnes PJ . Characterization of adenosine receptors in human pulmonary arteries. Am J Physiol 256: H41‐H46, 1989.
 404. McCormack DG , Rees RG , Crawley D , Barnes PJ , Evans TW . Sensory neuropeptides and hypoxic pulmonary vasoconstriction in the rat. Thorax 48: 554‐557, 1993.
 405. McCullagh A , Rosenthal M , Wanner A , Hurtado A , Padley S , Bush A . The bronchial circulation–worth a closer look: a review of the relationship between the bronchial vasculature and airway inflammation. Pediat Pulm 45: 1‐13, 2010.
 406. Mcloughlin P , Mcmurtry I . Counterpoint: Chronic hypoxia‐induced pulmonary hypertension does not lead to loss of pulmonary vasculature. J Appl Physiol 103: 1451‐1453; discussion 1453‐1454, 2007.
 407. McMahon TJ , Hood JS , Kadowitz PJ . Pulmonary vasodilator response to vagal stimulation is blocked by N omega‐nitro‐L‐arginine methyl ester in the cat. Circ Res 70: 364‐369, 1992.
 408. McMurtry IF . Angiotensin is not required for hypoxic constriction in salt solution‐perfused rat lungs. J Appl Physiol 56: 375‐380, 1984.
 409. McMurtry IF , Davidson AB , Reeves JT , Grover RF . Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs. Circ Res 38: 99‐104, 1976.
 410. McMurtry IV , Abe K , Ota H , Fagan KA , Oka M . Rho kinase‐mediated vasoconstriction in pulmonary hypertension. Adv Exp Med Biol 661: 299‐308, 2010.
 411. McMurtry MS , Bonnet S , Michelakis ED , Bonnet S , Haromy A , Archer SL . Statin therapy, alone or with rapamycin, does not reverse monocrotaline pulmonary arterial hypertension: the rapamycin‐atorvastatin‐simvastatin study. Am J Physiol Lung Cell Mol Physiol 293: L933‐L940, 2007.
 412. McMurtry MS , Bonnet S , Wu X , Dyck JR , Haromy A , Hashimoto K , Michelakis ED . Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res 95: 830‐840, 2004.
 413. Mehta D , Malik AB . Signaling mechanisms regulating endothelial permeability. Physiol Rev 86: 279, 2006.
 414. Mentzer RM, Jr. , Bartels C , Bolli R , Boyce S , Buckberg GD , Chaitman B , Haverich A , Knight J , Menasche P , Myers ML , Nicolau J , Simoons M , Thulin L , Weisel RD . Sodium‐hydrogen exchange inhibition by cariporide to reduce the risk of ischemic cardiac events in patients undergoing coronary artery bypass grafting: results of the EXPEDITION study. Ann Thorac Surg 85: 1261‐1270, 2008.
 415. Mentzer RM, Jr. , Rubio R , Berne RM . Release of adenosine by hypoxic canine lung tissue and its possible role in pulmonary circulation. Am J Physiol 229: 1625‐1631, 1975.
 416. Meyrick B , Gamble W , Reid L . Development of Crotalaria pulmonary hypertension: Hemodynamic and structural study. Am J Physiol 239: H692‐H702, 1980.
 417. Meyrick B , Niedermeyer ME , Ogletree ML , Brigham KL . Pulmonary hypertension and increased vasoreactivity caused by repeated indomethacin in sheep. J Appl Physiol (1985) 59: 443‐452, 1985.
 418. Michel RP . Arteries and veins of the normal dog lung: Qualitative and quantitative structural differences. Am J Anat 164: 227‐241, 1982.
 419. Michelakis ED , McMurtry MS , Wu XC , Dyck JR , Moudgil R , Hopkins TA , Lopaschuk GD , Puttagunta L , Waite R , Archer SL . Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: Role of increased expression and activity of voltage‐gated potassium channels. Circulation 105: 244‐250, 2002.
 420. Middelveld RJ , Alving K . Responses of the bronchial and pulmonary circulations to short‐term nitric oxide inhalation before and after endotoxaemia in the pig. Acta Physiol Scand 176: 71‐78, 2002.
 421. Mielke G , Benda N . Cardiac output and central distribution of blood flow in the human fetus. Circulation 103: 1662‐1668, 2001.
 422. Millan FA , Denhez F , Kondaiah P , Akhurst RJ . Embryonic gene expression patterns of TGF beta 1, beta 2 and beta 3 suggest different developmental functions in vivo. Development 111: 131‐143, 1991.
 423. Mitzner W , Lee W , Georgakopoulos D , Wagner E . Angiogenesis in the mouse lung. Am J Path 157: 93‐101, 2000.
 424. Mitzner W , Wagner E . On the purported discovery of the bronchial circulation by Leonardo da Vinci. J Appl Physiol 73: 1196‐1201, 1992.
 425. Mizuno S , Farkas L , Al Husseini A , Farkas D , Gomez‐Arroyo J , Kraskauskas D , Nicolls MR , Cool CD , Bogaard HJ , Voelkel NF . Severe pulmonary arterial hypertension induced by SU5416 and ovalbumin immunization. Am J Resp Cell Mol Biol 47: 679‐687, 2012.
 426. Mogami H , Kojima I . Stimulation of calcium entry is prerequisite for DNA synthesis induced by platelet‐derived growth factor in vascular smooth muscle cells. Biochem Biophys Res Commun 196: 650‐658, 1993.
 427. Moldobaeva A , Welsh‐Servinsky LE , Shimoda LA , Stephens RS , Verin AD , Tuder RM , Pearse DB . Role of protein kinase G in barrier‐protective effects of cGMP in human pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 290: L919‐L930, 2006.
 428. Morecroft I , Dempsie Y , Bader M , Walther DJ , Kotnik K , Loughlin L , Nilsen M , MacLean MR . Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia‐induced pulmonary hypertension. Hypertension 49: 232‐236, 2007.
 429. Morecroft I , Heeley RP , Prentice HM , Kirk A , MacLean MR . 5‐hydroxytryptamine receptors mediating contraction in human small muscular pulmonary arteries: Importance of the 5‐HT1B receptor. Br J Pharmacol 128: 730‐734, 1999.
 430. Morecroft I , Loughlin L , Nilsen M , Colston J , Dempsie Y , Sheward J , Harmar A , MacLean MR . Functional interactions between 5‐hydroxytryptamine receptors and the serotonin transporter in pulmonary arteries. J Pharmacol Exp Ther 313: 539‐548, 2005.
 431. Morgan JM , McCormack DG , Griffiths MJ , Morgan CJ , Barnes PJ , Evans TW . Adenosine as a vasodilator in primary pulmonary hypertension. Circulation 84: 1145‐1149, 1991.
 432. Morin FC, III , Egan EA . Pulmonary hemodynamics in fetal lambs during development at normal and increased oxygen tension. J Appl Physiol 73: 213‐218, 1992.
 433. Morio Y , Carter EP , Oka M , McMurtry IF . EDHF‐mediated vasodilation involves different mechanisms in normotensive and hypertensive rat lungs. Am J Physiol Heart Circ Physiol 284: H1762‐H1770, 2003.
 434. Morrell NW , Yang X , Upton PD , Jourdan KB , Morgan N , Sheares KK , Trembath RC . Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor‐β1 and bone morphogenetic proteins. Circulation 104: 790‐795, 2001.
 435. Morse JH , Jones AC , Barst RJ , Hodge SE , Wilhelmsen KC , Nygaard TG . Mapping of familial primary pulmonary hypertension locus (PPH1) to chromosome 2q31‐q32. Circulation 95: 2603‐2606, 1997.
 436. Moss AJ , Emmanouilides G , Duffie ER, Jr . Closure of the ductus arteriosus in the newborn infant. Pediatrics 32: 25‐30, 1963.
 437. Mura M , dos Santos CC , Stewart D , Liu M . Vascular endothelial growth factor and related molecules in acute lung injury. J Appl Physiol (1985) 97: 1605‐1617, 2004.
 438. Mure M , Domino KB , Lindahl SG , Hlastala MP , Altemeier WA , Glenny RW . Regional ventilation‐perfusion distribution is more uniform in the prone position. J Appl Physiol 88: 1076‐1083, 2000.
 439. Mure M , Nyren S , Jacobsson H , Larsson SA , Lindahl SG . High continuous positive airway pressure level induces ventilation/perfusion mismatch in the prone position. Crit Care Med 29: 959‐964, 2001.
 440. Murillo H , Cutalo MJ , Jones RP , Lane MJ , Fleischmann D , Restrepo CS . Pulmonary circulation imaging: Embryology and normal anatomy. Sem Ultrasound, CT, and MR 33: 473‐484, 2012.
 441. Murphy E , Allen DG . Why did the NHE inhibitor clinical trials fail? J Mol Cell Cardiol 46: 137‐141, 2009.
 442. Murray PA , Lodato RF , Michael JR . Neural antagonists modulate pulmonary vascular pressure‐flow plots in conscious dogs. J Appl Physiol (1985) 60: 1900‐1907, 1986.
 443. Murtha YM , Allen BM , Orr JA . The role of protein kinase C in thromboxane A2‐induced pulmonary artery vasoconstriction. J Biomed Sci 6: 293‐295, 1999.
 444. Musch G , Layfield JDH , Harris RS , Melo MFV , Winkler T , Callahan RJ , Fischman AJ , Venegas JGC . Topographical distribution of pulmonary perfusion and ventilation, assessed by PET in supine and prone humans. J Appl Physiol 93: 1841‐1851, 2002.
 445. Naeije R , Chesler NC . Pulmonary circulation at exercise. Compr Physiol 2: 711‐741, 2012.
 446. Naeye RL . Hypoxemia and pulmonary hypertension. A study of the pulmonary vasculature. Arch Pathol 71: 447‐452, 1961.
 447. Naeye RL . Children at high altitude: Pulmonary and renal abnormalities. Circ Res 16: 33‐38, 1965.
 448. Nagaoka T , Fagan KA , Gebb SA , Morris KG , Suzuki T , Shimokawa H , McMurtry IF , Oka M . Inhaled Rho kinase inhibitors are potent and selective vasodilators in rat pulmonary hypertension. Am J Resp Crit Care Med 171: 494‐499, 2005.
 449. Nagaoka T , Morio Y , Casanova N , Bauer N , Gebb S , McMurtry I , Oka M . Rho/Rho kinase signaling mediates increased basal pulmonary vascular tone in chronically hypoxic rats. Am J Physiol Lung Cell Mol Physiol 287: L665‐L672, 2004.
 450. Nagaoka T , Muramatsu M , Sato K , McMurtry I , Oka M , Fukuchi Y . Mild hypoxia causes severe pulmonary hypertension in fawn‐hooded but not in Tester Moriyama rats. Resp Physiol 127: 53‐60, 2001.
 451. Nakanishi R . Revascularization of trachea in lung and tracheal transplantation. Clin Transplant 21: 668‐674, 2007.
 452. Natarajan V , Dudek SM , Jacobson JR , Moreno‐Vinasco L , Huang LS , Abassi T , Mathew B , Zhao Y , Wang L , Bittman R , Weichselbaum R , Berdyshev E , Garcia JG . Sphingosine‐1‐phosphate, FTY720, and sphingosine‐1‐phosphate receptors in the pathobiology of acute lung injury. Am J Respir Cell Mol Biol 49: 6‐17, 2013.
 453. Neely CF , Kadowitz PJ , Lippton H , Neiman M , Hyman AL . Adenosine does not mediate the pulmonary vasodilator response of adenosine 5'‐triphosphate in the feline pulmonary vascular bed. J Pharmacol Exp Ther 250: 170‐176, 1989.
 454. Neely CF , Matot I , Batra VK , Bo X , Burnstock G . P2X purinoceptors in the feline pulmonary vascular bed: distribution and selective in vivo pharmacological probes. Am J Physiol 270: L889‐L897, 1996.
 455. Nelin LD , Dawson CA . The effect of N omega‐nitro‐L‐arginine methylester on hypoxic vasoconstriction in the neonatal pig lung. Pediatr Res 34: 349‐353, 1993.
 456. Newman JH , Holt TN , Hedges LK , Womack B , Memon SS , Willers ED , Wheeler L , Phillips JA, III , Hamid R . High‐altitude pulmonary hypertension in cattle (brisket disease): Candidate genes and gene expression profiling of peripheral blood mononuclear cells. Pulm Circ 1: 462‐469, 2011.
 457. Newman JH , Phillips JA , Loyd JE . Narrative review: The enigma of pulmonary arterial hypertension: New insights from genetic studies. Ann Intern Med 148: 278‐283, 2008.
 458. Ng LC , Wilson SM , Hume JR . Mobilization of sarcoplasmic reticulum stores by hypoxia leads to consequent activation of capacitative Ca2+ entry in isolated canine pulmonary arterial smooth muscle cells. J Physiol 563: 409‐419, 2005.
 459. Nichols WC , Koller DL , Slovis B , Foroud T , Terry VH , Arnold ND , Siemieniak DR , Wheeler L , Phillips JA, III , Newman JH , Conneally PM , Ginsburg D , Loyd JE . Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31‐32. Nat Gen 15: 277‐280, 1997.
 460. Norgaard MA , Alphonso N , Cochrane AD , Menahem S , Brizard CP , d'Udekem Y . Major aorto‐pulmonary collateral arteries of patients with pulmonary atresia and ventricular septal defect are dilated bronchial arteries. Eur J Cardio Surg 29: 653‐658, 2006.
 461. Nussenzveig DR , Lewicki JA , Maack T . Cellular mechanisms of the clearance function of type C receptors of atrial natriuretic factor. J Biol Chem 265: 20952‐20958, 1990.
 462. Nyhan DP , Chen BB , Fehr DM , Rock P , Murray PA . Anesthesia alters pulmonary vasoregulation by angiotensin II and captopril. J Appl Physiol 72: 636‐642, 1992.
 463. Nyrén S , Radell P , Lindahl SGE , Mure M , Petersson J , Larsson SA , Jacobsson H , Sánchez‐Crespo AC . Lung ventilation and perfusion in prone and supine postures with reference to anesthetized and mechanically ventilated healthy volunteers. Anesthesiology 112: 682‐687, 2010.
 464. Odell AF , Scott JL , Van Helden DF . EGF induces tyrosine phosphorylation, membrane insertion and activation of transient receptor potential channel 4. J Biol Chem 280: 37974‐37987, 2005.
 465. Oka M , Fagan KA , Jones PL , McMurtry IF . Therapeutic potential of RhoA/Rho kinase inhibitors in pulmonary hypertension. Br J Pharmacol 155: 444‐454, 2008.
 466. Oka M , Homma N , Taraseviciene‐Stewart L , Morris KG , Kraskauskas D , Burns N , Voelkel NF , McMurtry IF . Rho kinase‐mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats. Circ Res 100: 923‐929, 2007.
 467. Okada K , Tanaka Y , Bernstein M , Zhang W , Patterson GA , Botney MD . Pulmonary hemodynamics modify the rat pulmonary artery response to injury. A neointimal model of pulmonary hypertension. Am J Path 151: 1019‐1025, 1997.
 468. Osaki S , Nakanishi Y , Wataya H , Takayama K , Inoue K , Takaki Y , Murayama S , Hara N . Prognosis of bronchial artery embolization in the management of hemoptysis. Respiration 67: 412‐416, 2000.
 469. Oudiz RJ , Brundage BH , Galie N , Ghofrani HA , Simonneau G , Botros FT , Chan M , Beardsworth A , Barst RJ , Group PS . Tadalafil for the treatment of pulmonary arterial hypertension: A double‐blind 52‐week uncontrolled extension study. J Am Col Cardiol 60: 768‐774, 2012.
 470. Paddenberg R , Stieger P , Von Lilien A‐L , Faulhammer P , Goldenberg A , Tillmanns HH , Kummer W , Braun‐Dullaeus RC . Rapamycin attenuates hypoxia‐induced pulmonary vascular remodeling and right ventricular hypertrophy in mice. Respir Res 8: 15, 2007.
 471. Palmer LA , Johns RA . Hypoxia upregulates inducible (Type II) nitric oxide synthase in an HIF‐1 dependent manner in rat pulmonary microvascular but not aortic smooth muscle cells. Chest 114: 33S‐34S, 1998.
 472. Palmer LA , Semenza GL , Stoler MH , Johns RA . Hypoxia induces type II NOS gene expression in pulmonary artery endothelial cells via HIF‐1. Am J Physiol Lung Cell Mol Physiol 274: L212‐L219, 1998.
 473. Palmer RM , Ashton DS , Moncada S . Vascular endothelial cells synthesize nitric oxide from L‐arginine. Nature 333: 664‐666, 1988.
 474. Palmer RM , Ferrige AG , Moncada S . Nitric oxide release accounts for the biological activity of endothelium‐derived relaxing factor. Nature 327: 524‐526, 1987.
 475. Parera MC , van Dooren M , van Kempen M , de Krijger R , Grosveld F , Tibboel D , Rottier R . Distal angiogenesis: A new concept for lung vascular morphogenesis. Am J Physiol Lung Cell Mol Physiol 288: L141‐L149, 2005.
 476. Parker JC . Acute lung injury and pulmonary vascular permeability: Use of transgenic models. Compr Physiol 1: 835‐882.
 477. Parker JC , Stevens T , Randall J , Weber DS , King JA . Hydraulic conductance of pulmonary microvascular and macrovascular endothelial cell monolayers. Am J Physiol Lung Cell Mol Physiol 291: L30‐L37, 2006.
 478. Parker JC , Townsley MI . Evaluation of lung injury in rats and mice. Am J Physiol Lung Cell Mol Physiol 286: L231‐L246, 2004.
 479. Parker JC , Townsley MIC . Physiological determinants of the pulmonary filtration coefficient. Am J Physiol Lung Cell Mol Physiol 295: L235‐L237, 2008.
 480. Parker JC , Yoshikawa S . Vascular segmental permeabilities at high peak inflation pressure in isolated rat lungs. Am J Physiol Lung Cell Mol Physiol 283: L1203‐L1209, 2002.
 481. Parker RE , Granger DN , Taylor AE . Estimates of isogravimetric capillary pressures during alveolar hypoxia. Am J Physiol 241: H732‐H739, 1981.
 482. Parsons GH , Bommer WJ , Siefkin AD , Brock J , Lantz BM . Drainage routes of bronchial blood flow in anaesthetized sheep. Pulm Pharmacol Ther 20: 109‐111, 2007.
 483. Parthasarathi K , Ichimura H , Monma E , Lindert J , Quadri S , Issekutz A , Bhattacharya JCP . Connexin 43 mediates spread of Ca2+‐dependent proinflammatory responses in lung capillaries. J Clin Invest 116: 2193‐2200, 2006.
 484. Patterson GA , Todd TR , Cooper JD , Pearson FG , Winton TL , Maurer J . Airway complications after double lung transplantation. Toronto Lung Transplant Group. J Thoracic Cardiovasc Surg 99: 14‐20; discussion 20‐11, 1990.
 485. Pauling MH , Vu TH . Mechanisms and regulation of lung vascular development. Cur Topics Dev Biol 64: 73‐99, 2004.
 486. Pearl RG . Adenosine produces pulmonary vasodilation in the perfused rabbit lung via an adenosine A2 receptor. Anesth Analg 79: 46‐51, 1994.
 487. Pearl RG , Prielipp RC . Leukotriene synthesis inhibition and receptor blockade do not inhibit hypoxic pulmonary vasoconstriction in sheep. Anesth Analg 72: 169‐176, 1991.
 488. Pearson FG , Goldberg M , Stone RM , Colapinto RF . Bronchial arterial circulation restored after reimplantation of canine lung. Can J Surg 13: 243‐250, 1970.
 489. Pelage JP . Bronchial artery embolization: Anatomy and technique. Tech Vasc Intervent Radiol 10: 274‐275, 2007.
 490. Pelosi P , Tubiolo D , Mascheroni D , Vicardi P , Crotti S , Valenza F , Gattinoni L . Effects of the prone position on respiratory mechanics and gas exchange during acute lung injury. Am J Resp Crit Care Med 157: 387‐393, 1998.
 491. Pelton RW , Saxena B , Jones M , Moses HL , Gold LI . Immunohistochemical localization of TGF β1, TGF β2, and TGF β3 in the mouse embryo: Expression patterns suggest multiple roles during embryonic development. J Cell Biol 115: 1091‐1105, 1991.
 492. Penaloza D , Arias‐Stella J , Sime F , Recavarren S , Marticorena E . the heart and pulmonary circulation in children at high altitudes: Physiological, anatomical, and clinical observations. Pediatrics 34: 568‐582, 1964.
 493. Peng X , Hassoun PM , Sammani S , McVerry BJ , Burne MJ , Rabb H , Pearse D , Tuder RM , Garcia JG . Protective effects of sphingosine 1‐phosphate in murine endotoxin‐induced inflammatory lung injury. Am J Respir Crit Care Med 169: 1245‐1251, 2004.
 494. Permutt S , Bromberger‐Barnea B , Bane HN . Alveolar pressure, pulmonary venous pressure, and the vascular waterfall. Med Thorac 19: 239‐260, 1962.
 495. Petersson J , Rohdin M , Sánchez‐Crespo A , Nyrén S , Jacobsson H , Larsson SA , Lindahl SGE , Linnarsson D , Neradilek B , Polissar NL , Glenny RW , Mure MC . Posture primarily affects lung tissue distribution with minor effect on blood flow and ventilation. Respir Physiol Neurobiol 156: 293‐303, 2007.
 496. Pinheiro JM , Malik AB . Mechanisms of endothelin‐1‐induced pulmonary vasodilatation in neonatal pigs. J Physiol 469: 739‐752, 1993.
 497. Pisarcik S , Maylor J , Lu W , Yun X , Undem C , Sylvester JT , Semenza GL , Shimoda LA . Activation of hypoxia‐inducible factor‐1 in pulmonary arterial smooth muscle cells by endothelin‐1. Am J Physiol Lung Cell Mol Physiol 304: L549‐L561, 2013.
 498. Pluta RM , Oldfield EH , Bakhtian KD , Fathi AR , Smith RK , Devroom HL , Nahavandi M , Woo S , Figg WD , Lonser RR . Safety and feasibility of long‐term intravenous sodium nitrite infusion in healthy volunteers. PloS one 6: e14504, 2011.
 499. Porcelli RJ , Bergofsky EH . Adrenergic receptors in pulmonary vasoconstrictor responses to gaseous and humoral agents. J Appl Physiol 34: 483‐488, 1973.
 500. Porcelli RJ , Bergofsky EH . Effect of pH on pulmonary pressor responses to humoral agents. J Appl Physiol 31: 679‐685, 1971.
 501. Porta NF , Steinhorn RH . Pulmonary vasodilator therapy in the NICU: Inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents. Clin Perinat 39: 149‐164, 2012.
 502. Post JM , Gelband CH , Hume JR . [Ca2+]i inhibition of K+ channels in canine pulmonary artery. Novel mechanism for hypoxia‐induced membrane depolarization. Circ Res 77: 131‐139, 1995.
 503. Post JM , Hume JR , Archer SL , Weir EK . Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am J Physiol 262: C882‐C890, 1992.
 504. Pozeg ZI , Michelakis ED , McMurtry MS , Thebaud B , Wu XC , Dyck JR , Hashimoto K , Wang S , Moudgil R , Harry G , Sultanian R , Koshal A , Archer SL . In vivo gene transfer of the O2‐sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation 107: 2037‐2044, 2003.
 505. Prabhakar NR , Semenza GL . Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia‐inducible factors 1 and 2. Physiol Rev 92: 967‐1003, 2012.
 506. Prewitt RL , Leffler CW . Feline hypoxic pulmonary vasoconstriction is not blocked by the angiotensin I‐converting enzyme inhibitor, captopril. J Cardiovasc Pharmacol 3: 293‐298, 1981.
 507. Price LC , Wort SJ , Perros F , Dorfmuller P , Huertas A , Montani D , Cohen‐Kaminsky S , Humbert M . Inflammation in pulmonary arterial hypertension. Chest 141: 210‐221, 2012.
 508. Pullamsetti SS , Schermuly R , Ghofrani A , Weissmann N , Grimminger F , Seeger W . Novel and emerging therapies for pulmonary hypertension. Am J Resp Criti Care Med 189: 394‐400, 2014.
 509. Quinn DA , Dahlberg CG , Bonventre JP , Scheid CR , Honeyman T , Joseph PM , Thompson BT , Hales CA . The role of Na+/H+ exchange and growth factors in pulmonary artery smooth muscle cell proliferation. Am J Respir Cell Mol Biol 14: 139‐145, 1996.
 510. Quinn DA , Du HK , Thompson BT , Hales CA . Amiloride analogs inhibit chronic hypoxic pulmonary hypertension. Am J Respir Crit Care Med 157: 1263‐1268, 1998.
 511. Quinn DA , Honeyman TW , Joseph PM , Thompson BT , Hales CA , Scheid CR . Contribution of Na+/H+ exchange to pH regulation in pulmonary artery smooth muscle cells. Am J Respir Cell Mol Biol 5: 586‐591, 1991.
 512. Rabinovitch M , Chesler N , Molthen RC . Point:Counterpoint: Chronic hypoxia‐induced pulmonary hypertension does/does not lead to loss of pulmonary vasculature. J Appl Physiol 103: 1449‐1451, 2007.
 513. Rabinovitch M , Gamble WJ , Nadas AS , Miettinen OS , Reid L . Rat pulmonary circulation after chronic hypoxia: Hemodynamic and structural features. Am J Physiol 236: H818‐H827, 1979.
 514. Rabinovitch M , Guignabert C , Humbert M , Nicolls MR . Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension. Circ Res 115: 165‐175, 2014.
 515. Raj JU , Toga H , Ibe BO , Anderson J . Effects of endothelin, platelet activating factor and thromboxane A2 in ferret lungs. Respir Physiol 88: 129‐140, 1992.
 516. Rajagopalan B , Friend JA , Stallard T , Lee GD . Blood flow in pulmonary veins: II. The influence of events transmitted from the right and left sides of the heart. Cardiovasc Res 13: 677‐683, 1979.
 517. Rajaram SS , Desai NK , Kalra A , Gajera M , Cavanaugh SK , Brampton W , Young D , Harvey S , Rowan K . Pulmonary artery catheters for adult patients in intensive care. Cochrane Database Syst Rev 2: Cd003408, 2013.
 518. Rasanen J , Wood DC , Debbs RH , Cohen J , Weiner S , Huhta JC . Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy: A randomized study. Circulation 97: 257‐262, 1998.
 519. Rasanen J , Wood DC , Weiner S , Ludomirski A , Huhta JC . Role of the pulmonary circulation in the distribution of human fetal cardiac output during the second half of pregnancy. Circulation 94: 1068‐1073, 1996.
 520. Rathore R , Zheng YM , Niu CF , Liu QH , Korde A , Ho YS , Wang YX . Hypoxia activates NADPH oxidase to increase [ROS]i and [Ca2+]i through the mitochondrial ROS‐PKCepsilon signaling axis in pulmonary artery smooth muscle cells. Free Rad Biol Med 45: 1223‐1231, 2008.
 521. Rawat DK , Alzoubi A , Gupte R , Chettimada S , Watanabe M , Kahn AG , Okada T , McMurtry IF , Gupte SA . Increased reactive oxygen species, metabolic maladaptation, and autophagy contribute to pulmonary arterial hypertension‐induced ventricular hypertrophy and diastolic heart failure. Hypertension 64: 1266‐1274, 2014.
 522. Redding GJ , McMurtry I , Reeves JT . Effects of meclofenamate on pulmonary vascular resistance correlate with postnatal age in young piglets. Pediatr Res 18: 579‐583, 1984.
 523. Reid L . The angiogram and pulmonary artery structure and branching (in the normal and with reference to disease). Proc Royal Soc Med 58: 681‐684, 1965.
 524. Reid LM . Structure and function in pulmonary hypertension. New perceptions. Chest 89: 279‐288, 1986.
 525. Reid PG , Fraser AG , Watt AH , Henderson AH , Routledge PA . Acute haemodynamic effects of intravenous infusion of adenosine in conscious man. Eur Heart J 11: 1018‐1028, 1990.
 526. Remillard CV , Yuan JX . Activation of K+ channels: An essential pathway in programmed cell death. Am J Physiol Lung Cell Mol Physiol 286: L49‐L67, 2004.
 527. Rhodes J . Comparative physiology of hypoxic pulmonary hypertension: Historical clues from brisket disease. J Appl Physiol 98: 1092‐1100, 2005.
 528. Rich S , Kieras K , Hart K , Groves BM , Stobo JD , Brundage BH . Antinuclear antibodies in primary pulmonary hypertension. J Am Col Cardiol 8: 1307‐1311, 1986.
 529. Richardson JB . Nerve supply to the lungs. Am Rev Resp Dis 119: 785‐802, 1979.
 530. Richter T , Bellani G , Scott Harris R , Vidal Melo MF , Winkler T , Venegas JG , Musch GCP . Effect of prone position on regional shunt, aeration, and perfusion in experimental acute lung injury. Am J Resp Crit Care Med 172: 480‐487, 2005.
 531. Rios EJ , Fallon M , Wang J , Shimoda LA . Chronic hypoxia elevates intracellular pH and activates Na+/H+ exchange in pulmonary arterial smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 289(5): L867‐874, 2005.
 532. Rippe B , Rosengren BI , Carlsson O , Venturoli D . Transendothelial transport: The vesicle controversy. J Vasc Res 39: 375‐390, 2002.
 533. Rodman DM , Reese K , Harral J , Fouty B , Wu S , West J , Hoedt‐Miller M , Tada Y , Li KX , Cool C , Fagan K , Cribbs L . Low‐voltage‐activated (T‐type) calcium channels control proliferation of human pulmonary artery myocytes. Circ Res 96: 864‐872, 2005.
 534. Rodman DM , Yamaguchi T , O'Brien RF , McMurtry IF . Hypoxic contraction of isolated rat pulmonary artery. J Pharmacol Exp Therap 248: 952‐959, 1989.
 535. Roepke JE , Patterson CE , Packer CS , Rhoades RA . Response of perfused lung and isolated pulmonary artery to adenosine. Exp Lung Res 17: 25‐37, 1991.
 536. Rose JC , Kot PA , Cohn JN , Freis ED , Eckert GE . Comparison of effects of angiotensin and norepinephrine on pulmonary circulation, systemic arteries and veins, and systemic vascular capacity in the dog. Circulation 25: 247‐252, 1962.
 537. Rubin LJ , Galie N , Grimminger F , Grunig E , Humbert M , Jing ZC , Keogh A , Langleben D , Fritsch A , Menezes F , Davie N , Ghofrani HA . Riociguat for the treatment of pulmonary arterial hypertension: A long‐term extension study (PATENT‐2). Eur Respir J 45: 1303‐1313, 2015.
 538. Rudolph AM . Fetal and neonatal pulmonary circulation. Am Rev Resp Dis 115: 11‐18, 1977.
 539. Rudolph AM . Fetal and neonatal pulmonary circulation. Ann Rev Physiol 41: 383‐395, 1979.
 540. Rudolph AM . Aortopulmonary transposition in the fetus: Speculation on pathophysiology and therapy. Pediatr Res 61: 375‐380, 2007.
 541. Sanchez FA , Savalia NB , Duran RG , Lal BK , Boric MP , Duran WNC . Functional significance of differential eNOS translocation. Am J Physiol Heart Circ Physiol 291: H1058‐H1064, 2006.
 542. Sanchez T , Skoura A , Wu MT , Casserly B , Harrington EO , Hla T . Induction of vascular permeability by the sphingosine‐1‐phosphate receptor‐2 (S1P2R) and its downstream effectors ROCK and PTEN. Arterioscler Thromb Vasc Biol 27: 1312‐1318, 2007.
 543. Sasaki F , Pare P , Ernest D , Bai T , Verburgt L , March R , Baile E . Endogenous nitric oxide influences acetylcholine‐induced bronchovascular dilation in sheep. J Appl Physiol 78: 539‐545, 1995.
 544. Sato K , Webb S , Tucker A , Rabinovitch M , O'Brien RF , McMurtry IF , Stelzner TJ . Factors influencing the idiopathic development of pulmonary hypertension in the fawn hooded rat. Am Rev Resp Dis 145: 793‐797, 1992.
 545. Sato TN , Tozawa Y , Deutsch U , Wolburg‐Buchholz K , Fujiwara Y , Gendron‐Maguire M , Gridley T , Wolburg H , Risau W , Qin Y . Distinct roles of the receptor tyrosine kinases Tie‐1 and Tie‐2 in blood vessel formation. Nat 376: 70‐74, 1995.
 546. Satoh K , Fukumoto Y , Shimokawa H . Rho‐kinase: Important new therapeutic target in cardiovascular diseases. Am J Physiol Heart Circ Physiol 301: H287‐H296, 2011.
 547. Saueressig MG , Neto AM , Fortis EA , Westphal D , Edelweiss MI , Meurer L , Matte U . Vascular endothelial growth factor gene therapy induces early re‐establishment of canine bronchial circulation. Eur J Cardio Surg 33: 717‐722, 2008.
 548. Sayner SL . Emerging themes of cAMP regulation of the pulmonary endothelial barrier. Am J Physiol Lung Cell Mol Physiol 300: L667‐L678, 2011.
 549. Schermuly RT , Ghofrani HA , Wilkins MR , Grimminger F . Mechanisms of disease: Pulmonary arterial hypertension. Nat Rev Cardiol 8: 443‐455, 2011.
 550. Schlensak C , Doenst T , Preusser S , Wunderlich M , Kleinschmidt M , Beyersdorf F . Cardiopulmonary bypass reduction of bronchial blood flow: A potential mechanism for lung injury in a neonatal pig model. J Thor Cardiovasc Surg 123: 1199‐1205, 2002.
 551. Schmidt EP , Damarla M , Rentsendorj O , Servinsky LE , Zhu B , Moldobaeva A , Gonzalez A , Hassoun PM , Pearse DBCP . Soluble guanylyl cyclase contributes to ventilator‐induced lung injury in mice. Am J Physiol Lung Cell Mol Physiol 295: L1056‐L1065, 2008.
 552. Schmidt EP , Yang Y , Janssen WJ , Gandjeva A , Perez MJ , Barthel L , Zemans RL , Bowman JC , Koyanagi DE , Yunt ZX , Smith LP , Cheng SS , Overdier KH , Thompson KR , Geraci MW , Douglas IS , Pearse DB , Tuder RM . The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med 18: 1217‐1223, 2012.
 553. Schnurch H , Risau W . Expression of tie‐2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage. Development 119: 957‐968, 1993.
 554. Schraufnagel DE , Pearse DB , Mitzner WA , Wagner EM . Three‐dimensional structure of the bronchial microcirculation in sheep. Anatomical Rec 243: 357‐366, 1995.
 555. Schulze‐Neick I , Ho SY , Bush A , Rosenthal M , Franklin RC , Redington AN , Penny DJ . Severe airflow limitation after the unifocalization procedure: clinical and morphological correlates. Circulation 102: III142‐III147, 2000.
 556. Schulze‐Neick I , Penny DJ , Derrick GP , Dhillon R , Rigby ML , Kelleher A , Bush A , Redington AN . Pulmonary vascular‐bronchial interactions: Acute reduction in pulmonary blood flow alters lung mechanics. Heart 84: 284‐289, 2000.
 557. Scott JA , Craig I , McCormack DG . Nonadrenergic noncholinergic relaxation of human pulmonary arteries is partially mediated by nitric oxide. Am J Resp Crit Care Med 154: 629‐632, 1996.
 558. Scuri M , McCaskill V , Chediak AD , Abraham WM , Wanner A . Effect of inhaled and intravenous acetylcholine on bronchial blood flow in anesthetized sheep. J Appl Physiol 80: 341‐344, 1996.
 559. Selig WM , Noonan TC , Kern DF , Malik AB . Pulmonary microvascular responses to arachidonic acid in isolated perfused guinea pig lung. J Appl Physiol 60: 1972‐1979, 1986.
 560. Semenza GL , Wang GL . A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 12: 5447‐5454, 1992.
 561. Sequeira IM , Haberberger RV , Kummer W . Atrial and ventricular rat coronary arteries are differently supplied by noradrenergic, cholinergic and nitrergic, but not sensory nerve fibres. Ann Anat 187: 345‐355, 2005.
 562. Shalaby F , Rossant J , Yamaguchi TP , Gertsenstein M , Wu XF , Breitman ML , Schuh AC . Failure of blood‐island formation and vasculogenesis in Flk‐1‐deficient mice. Nature 376: 62‐66, 1995.
 563. Shao D , Park JE , Wort SJ . The role of endothelin‐1 in the pathogenesis of pulmonary arterial hypertension. Pharmacol Res 63: 504‐511, 2011.
 564. Shea BS , Brooks SF , Fontaine BA , Chun J , Luster AD , Tager AM . Prolonged exposure to sphingosine 1‐phosphate receptor‐1 agonists exacerbates vascular leak, fibrosis, and mortality after lung injury. Am J Respir Cell Mol Biol 43: 662‐673, 2010.
 565. Shimoda LA . 55th Bowditch Lecture: Effects of chronic hypoxia on the pulmonary circulation: Role of HIF‐1. J Appl Physiol 113: 1343‐1352, 2012.
 566. Shimoda LA , Fallon M , Pisarcik S , Wang J , Semenza GL . HIF‐1 regulates hypoxic induction of NHE1 expression and alkalinization of intracellular pH in pulmonary arterial myocytes. Am J Physiol Lung Cell Mol Physiol 291: L941‐L949, 2006.
 567. Shimoda LA , Laurie SS . Vascular remodeling in pulmonary hypertension. J Mol Med 91: 297‐309, 2013.
 568. Shimoda LA , Manalo DJ , Sham JS , Semenza GL , Sylvester JT . Partial HIF‐1α deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia. Am J Physiol Lung Cell Mol Physiol 281: L202‐L208, 2001.
 569. Shimoda LA , Polak J . Theme: Hypoxia hypoxia and ion channel function. Am J Physiol Cell Physiol 300(5): C951‐C967, 2011.
 570. Shimoda LA , Sham JS , Liu Q , Sylvester JT . Acute and chronic hypoxic pulmonary vasoconstriction: A central role for endothelin‐1? Respir Physiol Neurobiol 132: 93‐106, 2002.
 571. Shimoda LA , Sham JS , Shimoda TH , Sylvester JT . L‐type Ca2+ channels, resting [Ca2+]i, and ET‐1‐induced responses in chronically hypoxic pulmonary myocytes. Am J Physiol Lung Cell Mol Physiol 279: L884‐L894, 2000.
 572. Shimoda LA , Wang J , Sylvester JT . Ca2+ channels and chronic hypoxia. Microcirculation 13: 657‐670, 2006.
 573. Shimonaka M , Saheki T , Hagiwara H , Ishido M , Nogi A , Fujita T , Wakita K , Inada Y , Kondo J , Hirose S . Purification of atrial natriuretic peptide receptor from bovine lung. Evidence for a disulfide‐linked subunit structure. J Biol Chem 262: 5510‐5514, 1987.
 574. Shirai M , Shindo T , Shimouchi A , Ninomiya I . Diameter and flow velocity changes of feline small pulmonary vessels in response to sympathetic nerve stimulation. Pflugers Archiv 429: 267‐273, 1994.
 575. Shirley KL , Beckman DW , Garrick DJ . Inheritance of pulmonary arterial pressure in Angus cattle and its correlation with growth. J Animal Sci 86: 815‐819, 2008.
 576. Shu W , Jiang YQ , Lu MM , Morrisey EE . Wnt7b regulates mesenchymal proliferation and vascular development in the lung. Development 129: 4831‐4842, 2002.
 577. Sieber C , Kopf J , Hiepen C , Knaus P . Recent advances in BMP receptor signaling. Cytokine Growth Factor Rev 20: 343‐355, 2009.
 578. Siegelman SS , Hagstrom JW , Koerner SK , Veith FJ . Restoration of bronchial artery circulation after canine lung allotransplantation. J Thor Cardiovasc Surg 73: 792‐795, 1977.
 579. Siflinger‐Birnboim A , Del Vecchio PJ , Cooper JA , Blumenstock FA , Shepard JM , Malik AB . Molecular sieving characteristics of the cultured endothelial monolayer. J Cell Physiol 132: 111‐117, 1987.
 580. Silove ED , Inoue T , Grover RF . Comparison of hypoxia, pH, and sympathomimetic drugs on bovine pulmonary vasculature. J Appl Physiol 24: 355‐365, 1968.
 581. Simmons D , Linde L , Miller J , O'Reilly R . Relation between lung volume and pulmonary vascular resistance. Circ res 9: 465‐471, 1961.
 582. Simonneau G , D'Armini AM , Ghofrani HA , Grimminger F , Hoeper MM , Jansa P , Kim NH , Wang C , Wilkins MR , Fritsch A , Davie N , Colorado P , Mayer E . Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: A long‐term extension study (CHEST‐2). Eur Respir J 45: 1293‐1302, 2015.
 583. Simonson TS , Yang Y , Huff CD , Yun H , Qin G , Witherspoon DJ , Bai Z , Lorenzo FR , Xing J , Jorde LB , Prchal JT , Ge R . Genetic evidence for high‐altitude adaptation in Tibet. Science 329: 72‐75, 2010.
 584. Smirnov SV , Robertson TP , Ward JP , Aaronson PI . Chronic hypoxia is associated with reduced delayed rectifier K+ current in rat pulmonary artery muscle cells. Am J Physiol 266: H365‐H370, 1994.
 585. Smith TG , Brooks JT , Balanos GM , Lappin TR , Layton DM , Leedham DL , Liu C , Maxwell PH , McMullin MF , McNamara CJ , Percy MJ , Pugh CW , Ratcliffe PJ , Talbot NP , Treacy M , Robbins PA . Mutation of von Hippel‐Lindau tumour suppressor and human cardiopulmonary physiology. PLoS Med 3: e290, 2006.
 586. Sobol BJ , Bottex G , Emirgil C , Gissen H . Gaseous diffusion from alveoli to pulmonary vessels of considerable size. Circ Res 13: 71‐79, 1963.
 587. Song MY , Makino A , Yuan JX . STIM2 contributes to enhanced store‐operated ca entry in pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension. Pulm Circ 1: 84‐94, 2011.
 588. Song Y , Jones JE , Beppu H , Keaney JF , Loscalzo J , Zhang Y‐Y . Increased susceptibility to pulmonary hypertension in heterozygous BMPR2‐mutant mice. Circulation 112: 553‐562, 2005.
 589. Spalding MB , Ala‐Kokko TI , Kiviluoma K , Ruskoaho H , Alahuhta S . The hemodynamic effects of adenosine infusion after experimental right heart infarct in young swine. J Cardiovasc Pharmacol 35: 93‐99, 2000.
 590. Spiekerkoetter E , Sung YK , Sudheendra D , Bill M , Aldred MA , van de Veerdonk MC , Vonk Noordegraaf A , Long‐Boyle J , Dash R , Yang PC , Lawrie A , Swift AJ , Rabinovitch M , Zamanian RT . Low‐Dose FK506 (Tacrolimus) in end‐stage pulmonary arterial hypertension. Am J Resp Crit Care Med 192: 254‐257, 2015.
 591. Spiekerkoetter E , Tian X , Cai J , Hopper RK , Sudheendra D , Li CG , El‐Bizri N , Sawada H , Haghighat R , Chan R , Haghighat L , de Jesus Perez V , Wang L , Reddy S , Zhao M , Bernstein D , Solow‐Cordero DE , Beachy PA , Wandless TJ , Ten Dijke P , Rabinovitch M . FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension. J Clin Invest 123: 3600‐3613, 2013.
 592. Stenmark KR , Abman SH . Lung vascular development: Implications for the pathogenesis of bronchopulmonary dysplasia. Ann Rev Physiol 67: 623‐661, 2005.
 593. Stenmark KR , Fagan KA , Frid MG . Hypoxia‐induced pulmonary vascular remodeling: Cellular and molecular mechanisms. Circ Res 99: 675‐691, 2006.
 594. Stenmark KR , Fasules J , Hyde DM , Voelkel NF , Henson J , Tucker A , Wilson H , Reeves JT . Severe pulmonary hypertension and arterial adventitial changes in newborn calves at 4,300 m. J Appl Physiol 62: 821‐830, 1987.
 595. Stenmark KR , McMurtry IF . Vascular remodeling versus vasoconstriction in chronic hypoxic pulmonary hypertension: a time for reappraisal? Circ Res 97: 95‐98, 2005.
 596. Stenmark KR , Meyrick B , Galie N , Mooi WJ , McMurtry IF . Animal models of pulmonary arterial hypertension: The hope for etiological discovery and pharmacological cure. Am J Physiol Lung Cell Mol Physiol 297: L1013‐L1032, 2009.
 597. Stenmark KR , Rabinovitch M . Emerging therapies for the treatment of pulmonary hypertension. Pediatr Crit Care Med 11: S85‐S90, 2010.
 598. Stephens RS , Servinsky LE , Rentsendorj O , Kolb TM , Pfeifer A , Pearse DBCP . Protein kinase G increases antioxidant function in lung microvascular endothelial cells by inhibiting the c‐Abl tyrosine kinase. Am J Physiol Cell Physiol 306: C559‐C569, 2014.
 599. Stephenson AH , Sprague RS , Losapio JL , Lonigro AJ . Differential effects of 5,6‐EET on segmental pulmonary vasoactivity in the rabbit. Am J Physiol Heart Circ Physiol 284: H2153‐H2161, 2003.
 600. Stevens T . Functional and molecular heterogeneity of pulmonary endothelial cells. Proc Am Thorac Soc 8: 453‐457, 2011.
 601. Stevens T , Phan S , Frid MG , Alvarez D , Herzog E , Stenmark KR . Lung vascular cell heterogeneity: Endothelium, smooth muscle, and fibroblasts. Proc Am Thorac Soc 5: 783‐791, 2008.
 602. Stock KW , Chen Q , Levin D , Hatabu H , Edelman RR . Demonstration of gravity‐dependent lung perfusion with contrast‐enhanced magnetic resonance imaging. J Magn Reson Imaging 9: 557‐561, 1999.
 603. Storme L , Rairigh RL , Parker TA , Kinsella JP , Abman SH . In vivo evidence for a myogenic response in the fetal pulmonary circulation. Pediatr Res 45: 425‐431, 1999.
 604. Suri C , Jones PF , Patan S , Bartunkova S , Maisonpierre PC , Davis S , Sato TN , Yancopoulos GD . Requisite role of angiopoietin‐1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87: 1171‐1180, 1996.
 605. Suzuki H , Twarog BM . Membrane properties of smooth muscle cells in pulmonary hypertensive rats. Am J Physiol 242: H907‐H915, 1982.
 606. Sylvester JT , Shimoda LA , Aaronson PI , Ward JP . Hypoxic pulmonary vasoconstriction. Physiol Rev 92: 367‐520, 2012.
 607. Sylvin H , Weitzberg E , Alving K . Endothelin‐induced vascular and bronchial effects in pig airways: Role in acute allergic responses. J Appl Physiol 93: 1608‐1615, 2002.
 608. Szczepaniak WS , Zhang Y , Hagerty S , Crow MT , Kesari P , Garcia JG , Choi AM , Simon BA , McVerry BJ . Sphingosine 1‐phosphate rescues canine LPS‐induced acute lung injury and alters systemic inflammatory cytokine production in vivo. Transl Res 152: 213‐224, 2008.
 609. Tabakin BS , Hanson JS . Congenital absence of the aortic arch associated with patent ductus arteriosus and ventricular septal defect. Am J Cardiol 6: 689‐696, 1960.
 610. Tabeling C , Yu H , Wang L , Ranke H , Goldenberg NM , Zabini D , Noe E , Krauszman A , Gutbier B , Yin J , Schaefer M , Arenz C , Hocke AC , Suttorp N , Proia RL , Witzenrath M , Kuebler WM . CFTR and sphingolipids mediate hypoxic pulmonary vasoconstriction. Proc Nat Acad Sci U S A 112: E1614‐E1623, 2015.
 611. Tabuchi A , Styp‐Rekowska B , Slutsky AS , Wagner PD , Pries AR , Kuebler WM . Precapillary oxygenation contributes relevantly to gas exchange in the intact lung. Am J Resp Crit Care Med 188: 474‐481, 2013.
 612. Takahashi H , Goto N , Kojima Y , Tsuda Y , Morio Y , Muramatsu M , Fukuchi Y . Downregulation of type II bone morphogenetic protein receptor in hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 290: L450‐L458, 2006.
 613. Takahashi H , Ikeda T . Transcripts for two members of the transforming growth factor‐beta superfamily BMP‐3 and BMP‐7 are expressed in developing rat embryos. Dev Dynam 207: 439‐449, 1996.
 614. Tamaoki J , Sugimoto F , Tagaya E , Isono K , Chiyotani A , Konno K . Angiotensin II 1 receptor‐mediated contraction of pulmonary artery and its modulation by prolylcarboxypeptidase. J Appl Physiol 76: 1439‐1444, 1994.
 615. Tamby MC , Chanseaud Y , Humbert M , Fermanian J , Guilpain P , Garcia‐de‐la‐Pena‐Lefebvre P , Brunet S , Servettaz A , Weill B , Simonneau G , Guillevin L , Boissier MC , Mouthon L . Anti‐endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension. Thorax 60: 765‐772, 2005.
 616. Tamby MC , Humbert M , Guilpain P , Servettaz A , Dupin N , Christner JJ , Simonneau G , Fermanian J , Weill B , Guillevin L , Mouthon L . Antibodies to fibroblasts in idiopathic and scleroderma‐associated pulmonary hypertension. Eur Respir J 28: 799‐807, 2006.
 617. Tamosiuniene R , Tian W , Dhillon G , Wang L , Sung YK , Gera L , Patterson AJ , Agrawal R , Rabinovitch M , Ambler K , Long CS , Voelkel NF , Nicolls MR . Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension. Circ Res 109: 867‐879, 2011.
 618. Tan JZ , Kaley G , Gurtner GH . Nitric oxide and prostaglandins mediate vasodilation to 5,6‐EET in rabbit lung. Adv Exp Med Biol 407: 561‐566, 1997.
 619. Tan Q , Kerestes H , Percy MJ , Pietrofesa R , Chen L , Khurana TS , Christofidou‐Solomidou M , Lappin TR , Lee FS . Erythrocytosis and pulmonary hypertension in a mouse model of human HIF2A gain of function mutation. J Biol Chem 288: 17134‐17144, 2013.
 620. Tanaka Y , Schuster DP , Davis EC , Patterson GA , Botney MD . The role of vascular injury and hemodynamics in rat pulmonary artery remodeling. J Clin Invest 98:434‐442, 1996.
 621. Taraseviciene‐Stewart L , Kasahara Y , Alger L , Hirth P , Mc Mahon G , Waltenberger J , Voelkel NF , Tuder RM . Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death‐dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J 15: 427‐438, 2001.
 622. Taraseviciene‐Stewart L , Nicolls MR , Kraskauskas D , Scerbavicius R , Burns N , Cool C , Wood K , Parr JE , Boackle SA , Voelkel NF . Absence of T cells confers increased pulmonary arterial hypertension and vascular remodeling. Am J Resp Crit Care Med 175: 1280‐1289, 2007.
 623. Taraseviciene‐Stewart L , Scerbavicius R , Choe KH , Cool C , Wood K , Tuder RM , Burns N , Kasper M , Voelkel NF . Simvastatin causes endothelial cell apoptosis and attenuates severe pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 291: L668‐L676, 2006.
 624. Teerlink JR , Carteaux JP , Sprecher U , Loffler BM , Clozel M , Clozel JP . Role of endogenous endothelin in normal hemodynamic status of anesthetized dogs. Am J Physiol 268: H432‐H440, 1995.
 625. Teichert‐Kuliszewska K , Kutryk MJ , Kuliszewski MA , Karoubi G , Courtman DW , Zucco L , Granton J , Stewart DJ . Bone morphogenetic protein receptor‐2 signaling promotes pulmonary arterial endothelial cell survival: Implications for loss‐of‐function mutations in the pathogenesis of pulmonary hypertension. Circ Res 98: 209‐217, 2006.
 626. Thickett DR , Armstrong L , Christie SJ , Millar AB . Vascular endothelial growth factor may contribute to increased vascular permeability in acute respiratory distress syndrome. Am J Respir Crit Care Med 164: 1601‐1605, 2001.
 627. Thomas M . Pharmacological targets for pulmonary vascular disease: Vasodilation versus anti‐remodelling. Adv Exp Med Biol 661: 475‐490, 2010.
 628. Thomson JR , Machado RD , Pauciulo MW , Morgan NV , Humbert M , Elliott GC , Ward K , Yacoub M , Mikhail G , Rogers P , Newman J , Wheeler L , Higenbottam T , Gibbs JS , Egan J , Crozier A , Peacock A , Allcock R , Corris P , Loyd JE , Trembath RC , Nichols WC . Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR‐II, a receptor member of the TGF‐β family. J Med Genet 37: 741‐745, 2000.
 629. Thorin E , Clozel M . The cardiovascular physiology and pharmacology of endothelin‐1. Adv Pharmacol 60: 1‐26, 2010.
 630. Tian W , Jiang X , Tamosiuniene R , Sung YK , Qian J , Dhillon G , Gera L , Farkas L , Rabinovitch M , Zamanian RT , Inayathullah M , Fridlib M , Rajadas J , Peters‐Golden M , Voelkel NF , Nicolls MR . Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension. Sci Trans Med 5: 200ra117, 2013.
 631. Tiruppathi C , Ahmmed GU , Vogel SM , Malik AB . Ca2+ signaling, TRP channels, and endothelial permeability. Microcirculation 13: 693‐708, 2006.
 632. Tiruppathi C , Minshall RD , Paria BC , Vogel SM , Malik AB . Role of Ca2+ signaling in the regulation of endothelial permeability. Vascul Pharmacol 39: 173‐185, 2002.
 633. Toba M , Alzoubi A , O'Neill KD , Gairhe S , Matsumoto Y , Oshima K , Abe K , Oka M , McMurtry IF . Temporal hemodynamic and histological progression in Sugen5416/hypoxia/normoxia‐exposed pulmonary arterial hypertensive rats. Am J Physiol Heart Circ Physiol 306: H243‐H250, 2014.
 634. Townsley MI , King JA , Alvarez DF . Ca2+ channels and pulmonary endothelial permeability: Insights from study of intact lung and chronic pulmonary hypertension. Microcirculation 13: 725‐739, 2006.
 635. Townsley MI . Structure and composition of pulmonary arteries, capillaries, and veins. Compr Physiol 2: 675‐709, 2012.
 636. Troyanovsky B , Alvarez DF , King JA , Schaphorst KL . Thrombin enhances the barrier function of rat microvascular endothelium in a PAR‐1‐dependent manner. Am J Physiol Lung Cell Mol Physiol 294: L266‐L275, 2008.
 637. Tuder RM . Pathology of pulmonary arterial hypertension. Semin Respir Crit Care Med 30: 376‐385, 2009.
 638. Tuder RM , Groves B , Badesch DB , Voelkel NF . Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Path 144: 275‐285, 1994.
 639. Uchida K , Mizuno T , Shimonaka M , Sugiura N , Nara K , Ling N , Hagiwara H , Hirose S . Purification and properties of active atrial‐natriuretic‐peptide receptor (type C) from bovine lung. Biochem J 263: 671‐678, 1989.
 640. Uhlig S , Yang Y . Sphingolipids in acute lung injury. Handb Exp Pharmacol 2013(216): 227‐246.
 641. Uhlig S , Yang Y , Waade J , Wittenberg C , Babendreyer A , Kuebler WM . Differential regulation of lung endothelial permeability in vitro and in situ. Cell Physiol Biochem 34: 1‐19, 2014.
 642. Undem C , Rios EJ , Maylor J , Shimoda LA . Endothelin‐1 augments Na+/H+ exchange activity in murine pulmonary arterial smooth muscle cells via Rho kinase. PloS one 7: e46303, 2012.
 643. van den Bos GC , Westerhof N , Randall OS . Pulse wave reflection: can it explain the differences between systemic and pulmonary pressure and flow waves? A study in dogs. Circ Res 51: 479‐485, 1982.
 644. van Patot MC , Gassmann M . Hypoxia: Adapting to high altitude by mutating EPAS‐1, the gene encoding HIF‐2α. High Alt Med Biol 12: 157‐167, 2011.
 645. van Tuyl M , Liu J , Wang J , Kuliszewski M , Tibboel D , Post M . Role of oxygen and vascular development in epithelial branching morphogenesis of the developing mouse lung. Am J Physiol Lung Cell Mol Physiol 288: L167‐L178, 2005.
 646. Vandenbroucke E , Mehta D , Minshall R , Malik AB . Regulation of endothelial junctional permeability. Ann NY Acad Sci 1123: 134, 2008.
 647. Vanderpool RR , Kim AR , Molthen R , Chesler NC . Effects of acute Rho kinase inhibition on chronic hypoxia‐induced changes in proximal and distal pulmonary arterial structure and function. J Appl Physiol 110: 188‐198, 2011.
 648. Vergadi E , Chang MS , Lee C , Liang OD , Liu X , Fernandez‐Gonzalez A , Mitsialis SA , Kourembanas S . Early macrophage recruitment and alternative activation are critical for the later development of hypoxia‐induced pulmonary hypertension. Circulation 123: 1986‐1995, 2011.
 649. Viola AR , Abbate EH . Respiratory function and effective collateral flow 8 years after ligation of the left pulmonary artery. Am Rev Resp Dis 108: 1216‐1220, 1973.
 650. Voelkel NF , Tuder RM . Hypoxia‐induced pulmonary vascular remodeling: A model for what human disease? J Clin Invest 106: 733‐738, 2000.
 651. Vogel SM , Malik AB . Cytoskeletal dynamics and lung fluid balance. Compr Physiol 2: 449‐478, 2012.
 652. von Euler U , Liljestrand G . Observations on the pulmonary arterial blood pressure in the cat. Acta Phys Scandinav 12: 301‐320, 1946.
 653. Wagner EM , Brown RH . Blood flow distribution within the airway wall. J Appl Physiol 92: 1964‐1969, 2002.
 654. Wagner EM , Foster WM . Interdependence of bronchial circulation and clearance of 99mTc‐DTPA from the airway surface. J Appl Physiol 90: 1275‐1281, 2001.
 655. Wagner EM , Foster WM . The role of the bronchial vasculature in soluble particle clearance. Environ Health Perspect 109(Suppl 4): 563‐565, 2001.
 656. Wagner EM , Mitzner W , Brown RH . Site of functional bronchopulmonary anastomoses in sheep. Anatom Rec 254: 360‐366, 1999.
 657. Wagner JG , Roth RA . Neutrophil migration mechanisms, with an emphasis on the pulmonary vasculature. Pharmacol Rev 52: 349‐374, 2000.
 658. Walch L , Norel X , Gascard JP , Brink C . Functional studies of leukotriene receptors in vascular tissues. Am J Respir Crit Care Med 161: S107‐S111, 2000.
 659. Walker BR , Voelkel NF , Reeves JT . Pulmonary pressor response after prostaglandin synthesis inhibition in conscious dogs. J Appl Physiol Respir Environ Exerc Physiol 52: 705‐709, 1982.
 660. Walsh‐Sukys MC , Tyson JE , Wright LL , Bauer CR , Korones SB , Stevenson DK , Verter J , Stoll BJ , Lemons JA , Papile LA , Shankaran S , Donovan EF , Oh W , Ehrenkranz RA , Fanaroff AA . Persistent pulmonary hypertension of the newborn in the era before nitric oxide: Practice variation and outcomes. Pediatrics 105: 14‐20, 2000.
 661. Walther SM , Domino KB , Glenny RW , Hlastala MP . Positive end‐expiratory pressure redistributes perfusion to dependent lung regions in supine but not in prone lambs. Crit Care Med 27: 37‐45, 1999.
 662. Wang J , Juhaszova M , Rubin LJ , Yuan XJ . Hypoxia inhibits gene expression of voltage‐gated K+ channel a subunits in pulmonary artery smooth muscle cells. J Clin Invest 100: 2347‐2353, 1997.
 663. Wang J , Shimoda LA , Sylvester JT . Ca2+ responses of pulmonary arterial myocytes to acute hypoxia require release from ryanodine and inositol trisphosphate receptors in sarcoplasmic reticulum. Am J Physiol Lung Cell Mol Physiol 303: L161‐L168, 2012.
 664. Wang J , Shimoda LA , Weigand L , Wang W , Sun D , Sylvester JT . Acute hypoxia increases intracellular [Ca2+] in pulmonary arterial smooth muscle by enhancing capacitative Ca2+ entry. Am J Physiol Lung Cell Mol Physiol 288: L1059‐L1069, 2005.
 665. Wang J , Weigand L , Foxson J , Shimoda LA , Sylvester JT . Ca2+ signaling in hypoxic pulmonary vasoconstriction: effects of myosin light chain and Rho kinase antagonists. Am J Physiol Lung Cell Mol Physiol 293: L674‐L685, 2007.
 666. Wang J , Weigand L , Lu W , Sylvester JT , Semenza GL , Shimoda LA . Hypoxia inducible factor 1 mediates hypoxia‐induced TRPC expression and elevated intracellular Ca2+ in pulmonary arterial smooth muscle cells. Circ Res 98: 1528‐1537, 2006.
 667. Wang J , Yang K , Xu L , Zhang Y , Lai N , Jiang H , Zhang Y , Zhong N , Ran P , Lu W . Sildenafil inhibits hypoxia‐induced transient receptor potential canonical protein expression in pulmonary arterial smooth muscle via cGMP‐PKG‐PPARgamma axis. Am J Respir Cell Mol Biol 49: 231‐240, 2013.
 668. Wang L , Dudek SMC . Regulation of vascular permeability by sphingosine 1‐phosphate. Microvasc Res 77: 39‐45, 2009.
 669. Wang L , Yin J , Nickles HT , Ranke H , Tabuchi A , Hoffmann J , Tabeling C , Barbosa‐Sicard E , Chanson M , Kwak BR , Shin HS , Wu S , Isakson BE , Witzenrath M , de Wit C , Fleming I , Kuppe H , Kuebler WM . Hypoxic pulmonary vasoconstriction requires connexin 40‐mediated endothelial signal conduction. J Clin Invest 122: 4218‐4230, 2012.
 670. Wang le F , Patel M , Razavi HM , Weicker S , Joseph MG , McCormack DG , Mehta S . Role of inducible nitric oxide synthase in pulmonary microvascular protein leak in murine sepsis. Am J Resp Crit Care Med 165: 1634‐1639, 2002.
 671. Ward JPT , Mcmurtry IF . Mechanisms of hypoxic pulmonary vasoconstriction and their roles in pulmonary hypertension: New findings for an old problem. Cur Opin Pharmacol 9: 287‐296, 2009.
 672. Warrell DA , Evans JW , Clarke RO , Kingaby GP , West JBC . Pattern of filling in the pulmonary capillary bed. J Appl Physiol 32: 346‐356, 1972.
 673. Warren RL , Powell WJ, Jr . Acute alveolar hypoxia increases bronchopulmonary shunt flow in the dog. J Clin Invest 77: 1515‐1524, 1986.
 674. Waypa GB , Chandel NS , Schumacker PT . Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing. Circ Res 88: 1259‐1266, 2001.
 675. Waypa GB , Guzy R , Mungai PT , Mack MM , Marks JD , Roe MW , Schumacker PT . Increases in mitochondrial reactive oxygen species trigger hypoxia‐induced calcium responses in pulmonary artery smooth muscle cells. Circ Res 99: 970‐978, 2006.
 676. Waypa GB , Marks JD , Guzy R , Mungai PT , Schriewer J , Dokic D , Schumacker PT . Hypoxia triggers subcellular compartmental redox signaling in vascular smooth muscle cells. Circ Res 106: 526‐535, 2010.
 677. Waypa GB , Marks JD , Mack MM , Boriboun C , Mungai PT , Schumacker PT . Mitochondrial reactive oxygen species trigger calcium increases during hypoxia in pulmonary arterial myocytes. Circ Res 91: 719‐726, 2002.
 678. Weibel ER . Morphological basis of alveolar‐capillary gas exchange. Physiol Rev 53: 419‐495, 1973.
 679. Weigand L , Foxson J , Wang J , Shimoda LA , Sylvester JT . Inhibition of hypoxic pulmonary vasoconstriction by antagonists of store‐operated Ca2+ and nonselective cation channels. Am J Physiol Lung Cell Mol Physiol 289: L5‐L13, 2005.
 680. Weir EK , McMurtry IF , Tucker A , Reeves JT , Grover RF . Prostaglandin synthetase inhibitors do not decrease hypoxic pulmonary vasoconstriction. J Appl Physiol 41: 714‐718, 1976.
 681. Weir EK , Tucker A , Reeves JT , Will DH , Grover RF . The genetic factor influencing pulmonary hypertension in cattle at high altitude. Cardiovasc Res 8: 745‐749, 1974.
 682. Weissmann N , Voswinckel R , Hardebusch T , Rosseau S , Ghofrani HA , Schermuly R , Seeger W , Grimminger F . Evidence for a role of protein kinase C in hypoxic pulmonary vasoconstriction. Am J Physiol 276: L90‐L95, 1999.
 683. Weitzberg E , Hemsen A , Rudehill A , Modin A , Wanecek M , Lundberg JM . Bosentan‐improved cardiopulmonary vascular performance and increased plasma levels of endothelin‐1 in porcine endotoxin shock. Br J Pharmacol 118: 617‐626, 1996.
 684. West J , Fagan K , Steudel W , Fouty B , Lane K , Harral J , Hoedt‐Miller M , Tada Y , Ozimek J , Tuder R , Rodman DM . Pulmonary hypertension in transgenic mice expressing a dominant‐negative BMPRII gene in smooth muscle. Circ Res 94: 1109‐1114, 2004.
 685. West J , Hemnes A . Experimental and transgenic models of pulmonary hypertension. Compr Physiol 1: 769‐782, 2011.
 686. West JB . Comparative physiology of the pulmonary circulation. Compr Physiol 1: 1525‐1539, 2011.
 687. West JB . Fragility of pulmonary capillaries. J Appl Physiol 115: 1‐15, 2013.
 688. West JB , Dollery CT , Naimark A . Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures. J Appl Physiol 19: 713‐724, 1964.
 689. Wharton J , Strange JW , Moller GM , Growcott EJ , Ren X , Franklyn AP , Phillips SC , Wilkins MR . Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med 172: 105‐113, 2005.
 690. White K , Dempsie Y , Nilsen M , Wright AF , Loughlin L , MacLean MR . The serotonin transporter, gender, and 17β oestradiol in the development of pulmonary arterial hypertension. Cardiovasc Res 90: 373‐382, 2011.
 691. Whitman EM , Pisarcik S , Luke T , Fallon M , Wang J , Sylvester JT , Semenza GL , Shimoda LA . Endothelin‐1 mediates hypoxia‐induced inhibition of voltage‐gated K+ channel expression in pulmonary arterial myocytes. Am J Physiol Lung Cell Mol Physiol 294: L309‐L318, 2008.
 692. Wicks TC , Rose JC , Johnson M , Ramwell PW , Kot PA . Vascular responses to arachidonic acid in the perfused canine lung. Circ Res 38: 167‐171, 1976.
 693. Wiener CM , Kirk W , Albert RK . Prone position reverses gravitational distribution of perfusion in dog lungs with oleic acid‐induced injury. J Appl Physiol 68: 1386‐1392, 1990.
 694. Wiener F , Morkin E , Skalak R , Fishman AP . Wave propagation in the pulmonary circulation. Circ Res 19: 834‐850, 1966.
 695. Wiklund NP , Cederqvist B , Matsuda H , Gustafsson LE . Adenosine can excite pulmonary artery. Acta Physiol Scand 131: 477‐478, 1987.
 696. Wilkins MR , Ali O , Bradlow W , Wharton J , Taegtmeyer A , Rhodes CJ , Ghofrani HA , Howard L , Nihoyannopoulos P , Mohiaddin RH , Gibbs JS , Simvastatin Pulmonary Hypertension Trial Study G. Simvastatin as a treatment for pulmonary hypertension trial. Am J Resp Crit Care Med 181: 1106‐1113, 2010.
 697. Wilkinson M , Langhorne CA , Heath D , Barer GR , Howard P . A pathophysiological study of 10 cases of hypoxic cor pulmonale. Q J Med 66: 65‐85, 1988.
 698. Will DH , Hicks JL , Card CS , Alexander AF . Inherited susceptibility of cattle to high‐altitude pulmonary hypertension. J Appl Physiol 38: 491‐494, 1975.
 699. Williams AE , Chambers RCCP . The mercurial nature of neutrophils: Still an enigma in ARDS? Am J Physiol Lung Cell Mol Physiol 306: L217‐L230, 2014.
 700. Winters JW , Wong J , Van Dyke D , Johengen M , Heymann MA , Fineman JR . Endothelin receptor blockade does not alter the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs. Pediatr Res 40: 152‐157, 1996.
 701. Wojciak‐Stothard B , Haworth SG . Perinatal changes in pulmonary vascular endothelial function. Pharmacol Ther 109: 78‐91, 2006.
 702. Wojciak‐Stothard B , Zhao L , Oliver E , Dubois O , Wu Y , Kardassis D , Vasilaki E , Huang M , Mitchell JA , Harrington LS , Prendergast GC , Wilkins MR . Role of RhoB in the regulation of pulmonary endothelial and smooth muscle cell responses to hypoxia. Circ Res 110: 1423‐1434, 2012.
 703. Wright JL , Petty T , Thurlbeck WM . Analysis of the structure of the muscular pulmonary arteries in patients with pulmonary hypertension and COPD: National Institutes of Health nocturnal oxygen therapy trial. Lung 170: 109‐124, 1992.
 704. Xu W , Koeck T , Lara AR , Neumann D , DiFilippo FP , Koo M , Janocha AJ , Masri FA , Arroliga AC , Jennings C , Dweik RA , Tuder RM , Stuehr DJ , Erzurum SC . Alterations of cellular bioenergetics in pulmonary artery endothelial cells. Proc Nat Acad Sci U S A 104: 1342‐1347, 2007.
 705. Yadav VR , Song T , Joseph L , Mei L , Zheng YM , Wang YX . Important role of PLC‐gamma1 in hypoxic increase in intracellular calcium in pulmonary arterial smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 304: L143‐L151, 2013.
 706. Yaghi A , Webb CD , Scott JA , Mehta S , Bend JR , McCormack DG . Cytochrome P450 metabolites of arachidonic acid but not cyclooxygenase‐2 metabolites contribute to the pulmonary vascular hyporeactivity in rats with acute Pseudomonas pneumonia. J Pharmacol Exp Ther 297: 479‐488, 2001.
 707. Yamamoto H , Yun EJ , Gerber HP , Ferrara N , Whitsett JA , Vu TH . Epithelial‐vascular cross talk mediated by VEGF‐A and HGF signaling directs primary septae formation during distal lung morphogenesis. Dev Biol 308: 44‐53, 2007.
 708. Yan W , Wu F , Morser J , Wu Q . Corin, a transmembrane cardiac serine protease, acts as a pro‐atrial natriuretic peptide‐converting enzyme. Proc Nat Acad Sci U S A 97: 8525‐8529, 2000.
 709. Yanagisawa M , Kurihara H , Kimura S , Goto K , Masaki T . A novel peptide vasoconstrictor, endothelin, is produced by vascular endothelium and modulates smooth muscle Ca2+ channels. J Hypertens Suppl 6: S188‐S191, 1988.
 710. Yang C , Jiang L , Zhang H , Shimoda LA , DeBerardinis RJ , Semenza GL . Analysis of hypoxia‐induced metabolic reprogramming. Methods Enzymol 542: 425‐455, 2014.
 711. Yang J , Li X , Al‐Lamki R , Wu C , Weiss A , Berk J , Schermuly RT , Morrell NW . Sildenafil potentiates bone morphogenetic protein signaling in pulmonary arterial smooth muscle cells and in experimental pulmonary hypertension. Arterioscler Thromb Vasc Biol 33: 34‐42, 2013.
 712. Yang X , Castilla LH , Xu X , Li C , Gotay J , Weinstein M , Liu PP , Deng CX . Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development 126: 1571‐1580, 1999.
 713. Yang X , Lee PJ , Long L , Trembath RC , Morrell NW . BMP4 induces HO‐1 via a Smad‐independent, p38MAPK‐dependent pathway in pulmonary artery myocytes. Am J Respir Cell Mol Biol 37: 598‐605, 2007.
 714. Yang X , Long L , Southwood M , Rudarakanchana N , Upton PD , Jeffery TK , Atkinson C , Chen H , Trembath RC , Morrell NW . Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Circ Res 96: 1053‐1063, 2005.
 715. Yang Y , Schmidt EPC . The endothelial glycocalyx: An important regulator of the pulmonary vascular barrier. Tissue Barriers 1: pii: 23494, 2013.
 716. Yi X , Liang Y , Huerta‐Sanchez E , Jin X , Cuo ZX , Pool JE , Xu X , Jiang H , Vinckenbosch N , Korneliussen TS , Zheng H , Liu T , He W , Li K , Luo R , Nie X , Wu H , Zhao M , Cao H , Zou J , Shan Y , Li S , Yang Q , Asan, Ni P , Tian G , Xu J , Liu X , Jiang T , Wu R , Zhou G , Tang M , Qin J , Wang T , Feng S , Li G , Huasang, Luosang J , Wang W , Chen F , Wang Y , Zheng X , Li Z , Bianba Z , Yang G , Wang X , Tang S , Gao G , Chen Y , Luo Z , Gusang L , Cao Z , Zhang Q , Ouyang W , Ren X , Liang H , Zheng H , Huang Y , Li J , Bolund L , Kristiansen K , Li Y , Zhang Y , Zhang X , Li R , Li S , Yang H , Nielsen R , Wang J , Wang J . Sequencing of 50 human exomes reveals adaptation to high altitude. Science 329: 75‐78, 2010.
 717. Ying X , Minamiya Y , Fu C , Bhattacharya J . Ca2+ waves in lung capillary endothelium. Circ Res 79: 898, 1996.
 718. Yoon W , Kim YH , Kim JK , Kim YC , Park JG , Kang HK . Massive hemoptysis: Prediction of nonbronchial systemic arterial supply with chest CT. Radiology 227: 232‐238, 2003.
 719. Yu AY , Shimoda LA , Iyer NV , Huso DL , Sun X , McWilliams R , Beaty T , Sham JS , Wiener CM , Sylvester JT , Semenza GL . Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia‐inducible factor 1α. J Clin Invest 103: 691‐696, 1999.
 720. Yu L , Hales CA . Silencing of NHE1 attenuates PASMC proliferation, hypertrophy and migration via E2F1. Am J Respir Cell Mol Biol 45: 923‐930, 2011.
 721. Yu L , Quinn DA , Garg HG , Hales CA . Deficiency of the NHE1 gene prevents hypoxia‐induced pulmonary hypertension and vascular remodeling. Am J Respir Crit Care Med 177: 1276‐1284, 2008.
 722. Yu M , McAndrew RP , Al‐Saghir R , Maier KG , Medhora M , Roman RJ , Jacobs ER . Nitric oxide contributes to 20‐HETE‐induced relaxation of pulmonary arteries. J Appl Physiol 93: 1391‐1399, 2002.
 723. Yu Y , Fantozzi I , Remillard CV , Landsberg JW , Kunichika N , Platoshyn O , Tigno DD , Thistlethwaite PA , Rubin LJ , Yuan JX . Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci U S A 101: 13861‐13866, 2004.
 724. Yu Y , Keller SH , Remillard CV , Safrina O , Nicholson A , Zhang SL , Jiang W , Vangala N , Landsberg JW , Wang JY , Thistlethwaite PA , Channick RN , Robbins IM , Loyd JE , Ghofrani HA , Grimminger F , Schermuly RT , Cahalan MD , Rubin LJ , Yuan JX . A functional single‐nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension. Circulation 119: 2313‐2322, 2009.
 725. Yuan JX , Aldinger AM , Juhaszova M , Wang J , Conte JV, Jr. , Gaine SP , Orens JB , Rubin LJ . Dysfunctional voltage‐gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension. Circulation 98: 1400‐1406, 1998.
 726. Yuan SY . New insights into eNOS signaling in microvascular permeability. Am J Physiol Heart Circ Physiol 291:H1029‐1031, 2006.
 727. Yuan SY , Rigor RR . Methods for measuring permeability. In: Yuan SY , Rigor RR , editors. Regulation of Endothelial Barrier Function. San Rafael (CA): Morgan and Claypool Lifesciences, 2010.
 728. Yuan XJ , Goldman WF , Tod ML , Rubin LJ , Blaustein MP . Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes. Am J Physiol 264: L116‐L123, 1993.
 729. Yuan XJ , Tod ML , Rubin LJ , Blaustein MP . Hypoxic and metabolic regulation of voltage‐gated K+ channels in rat pulmonary artery smooth muscle cells. Exp Physiol 80: 803‐813, 1995.
 730. Yuan XJ , Wang J , Juhaszova M , Gaine SP , Rubin LJ . Attenuated K+ channel gene transcription in primary pulmonary hypertension. Lancet 351: 726‐727, 1998.
 731. Zeldin DC , Foley J , Ma J , Boyle JE , Pascual JM , Moomaw CR , Tomer KB , Steenbergen C , Wu S . CYP2J subfamily P450s in the lung: Expression, localization, and potential functional significance. Mol Pharmacol 50: 1111‐1117, 1996.
 732. Zhang RZ , Yang Q , Yim AP , Huang Y , He GW . Role of NO and EDHF‐mediated endothelial function in the porcine pulmonary circulation: Comparison between pulmonary artery and vein. Vascul Pharmacol 44: 183‐191, 2006.
 733. Zhao L , Sebkhi A , Ali O , Wojciak‐Stothard B , Mamanova L , Yang Q , Wharton J , Wilkins MR . Simvastatin and sildenafil combine to attenuate pulmonary hypertension. Eur Respir J 34: 948‐957, 2009.
 734. Zhao Y , Young SL . Expression of transforming growth factor‐beta type II receptor in rat lung is regulated during development. Am J Physiol 269: L419‐L426, 1995.
 735. Zhou H , Gao Y , Raj JU . Antenatal betamethasone therapy augments nitric oxide‐mediated relaxation of preterm ovine pulmonary veins. J Appl Physiol 80: 390‐396, 1996.
 736. Zhu D , Bousamra M, II , Zeldin DC , Falck JR , Townsley M , Harder DR , Roman RJ , Jacobs ER . Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 278: L335‐L343, 2000.
 737. Zhu D , Zhang C , Medhora M , Jacobs ER . CYP4A mRNA, protein, and product in rat lungs: novel localization in vascular endothelium. J Appl Physiol 93: 330‐337, 2002.
 738. Zuckerbraun BS , George P , Gladwin MT . Nitrite in pulmonary arterial hypertension: Therapeutic avenues in the setting of dysregulated arginine/nitric oxide synthase signalling. Cardiovas Res 89: 542‐552, 2011.
 739. Zuckerbraun BS , Shiva S , Ifedigbo E , Mathier MA , Mollen KP , Rao J , Bauer PM , Choi JJ , Curtis E , Choi AM , Gladwin MT . Nitrite potently inhibits hypoxic and inflammatory pulmonary arterial hypertension and smooth muscle proliferation via xanthine oxidoreductase‐dependent nitric oxide generation. Circulation 121: 98‐109, 2010.

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Karthik Suresh, Larissa A. Shimoda. Lung Circulation. Compr Physiol 2016, 6: 897-943. doi: 10.1002/cphy.c140049