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Autonomic Factors in Hyperreactivity of Airway Smooth Muscle

J. A. Nadel, P. J. Barnes, M. J. Holtzman

10.1002/cphy.cp030338

Source: Supplement 12: Handbook of Physiology, The Respiratory System, Mechanics of Breathing

Originally published: 1986

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Sympathetic Nervous System
1.1 Sympathetic Innervation
1.2 Circulating Catecholamines
1.3 β‐Receptors
1.4 α‐Receptors
2 Nonadrenergic Inhibitory Nervous System
3 Parasympathetic Nervous System
3.1 General Considerations
3.2 Altered Parasympathetic Activity
3.3 Studies of Asthmatic Patients
4 Conclusion
Figure 1. Figure 1.

Sympathetic, parasympathetic, and nonadrenergic inhibitory nervous pathways from central nervous system to airway smooth muscle. Sympathetic pathway includes motor nerves, which travel to sympathetic ganglia and release acetylcholine (ACh), which stimulates nicotinic receptors (N) in the ganglia, and postganglionic nerves, which may travel to parasympathetic ganglia (—) and to airway smooth muscle and release norepinephrine (NE). Present evidence suggests that sympathetic nerves innervate ganglia and blood vessels, but not airway smooth muscle, in humans. Thus NE could bind to α‐receptors (α) in parasympathetic ganglia and thereby inhibit ganglionic transmission and decrease parasympathetic muscle tone; NE (e.g., released from bronchial arteries) could also bind to α‐receptors (α) on airway smooth muscle, causing muscle contraction, or bind to β‐receptors (β), causing muscle relaxation. Parasympathetic pathway includes motor nerves, which travel in vagus nerves to parasympathetic ganglia and release ACh, and postganglionic nerves, which release ACh that in turn binds to muscarinic receptors (M) on smooth muscle, causing contraction. For nonadrenergic inhibitory pathway, anatomy and transmitters are not defined precisely but may include motor nerves, which travel in vagus nerves, and postganglionic nerves, which release a neuropeptide [e.g., vasoactive intestinal peptide (VIP)] that binds to peptidergic receptors causing relaxation. EPI, epinephrine.


Figure 1.

Sympathetic, parasympathetic, and nonadrenergic inhibitory nervous pathways from central nervous system to airway smooth muscle. Sympathetic pathway includes motor nerves, which travel to sympathetic ganglia and release acetylcholine (ACh), which stimulates nicotinic receptors (N) in the ganglia, and postganglionic nerves, which may travel to parasympathetic ganglia (—) and to airway smooth muscle and release norepinephrine (NE). Present evidence suggests that sympathetic nerves innervate ganglia and blood vessels, but not airway smooth muscle, in humans. Thus NE could bind to α‐receptors (α) in parasympathetic ganglia and thereby inhibit ganglionic transmission and decrease parasympathetic muscle tone; NE (e.g., released from bronchial arteries) could also bind to α‐receptors (α) on airway smooth muscle, causing muscle contraction, or bind to β‐receptors (β), causing muscle relaxation. Parasympathetic pathway includes motor nerves, which travel in vagus nerves to parasympathetic ganglia and release ACh, and postganglionic nerves, which release ACh that in turn binds to muscarinic receptors (M) on smooth muscle, causing contraction. For nonadrenergic inhibitory pathway, anatomy and transmitters are not defined precisely but may include motor nerves, which travel in vagus nerves, and postganglionic nerves, which release a neuropeptide [e.g., vasoactive intestinal peptide (VIP)] that binds to peptidergic receptors causing relaxation. EPI, epinephrine.

References
 1. Andersson, R., K. Nilsson, J. Wikberg, S. Johansson, and L. Lundholm. Cyclic nucleotides and the contraction of smooth muscle. In: Advances in Cyclic Nucleotides Research, edited by G. I. Drummond, P. Greengard, and G. A. Robison. New York: Raven, 1975, p. 491–518.
 2. Apold, J., and L. Aksnes. Correlation between increased bronchial responsiveness to histamine and diminished plasma cyclic adenosine monophosphate response after epinephrine in asthmatic children. J. Allergy Clin. Immunol. 59: 343–347, 1977.
 3. Avner, B. P., and J. W. Jenne. Comparison of in vitro isoproterenol induced desensitization in human, dog, rat and rabbit respiratory smooth muscle (Abstract). Am. Rev. Respir. Dis. 115: 45A, 1977.
 4. Baker, D. G., R. A. Mitchell, and D. A. Herbert. Control of airway smooth muscle: role of sympathetic nervous system. In: Proceedings of Modelling and Control of Breathing, edited by B. J. Whipp and M. Wiberg. Amsterdam: Elsevier, 1982, p. 150–159.
 5. Bandouvakis, J., A. Cartier, R. Roberts, G. Ryan, and F. E. Hargreave. The effect of ipratropium and fenoterol on methacholine‐ and histamine‐induced bronchoconstriction. Br. J. Dis. Chest 75: 295–305, 1981.
 6. Barnes, P. J., C. B. Basbaum, J. A. Nadel, and J. M. Roberts. Localization of β‐adrenoceptors in mammalian lung by light microscopic autoradiography. Nature London 299: 444–447, 1982.
 7. Barnes, P. J., C. B. Basbaum, J. A. Nadel, and J. M. roberts. Pulmonary alpha‐adrenoceptors: autoradiographic localization using 3H prazosin. Eur. J. Pharmacol. 88: 57–62, 1983.
 8. Barnes, P. J., M. J. Brown, M. Silverman, and C. T. Dollery. Circulating catecholamines in exercise and hyperventilation induced asthma. Thorax 36: 435–440, 1981.
 9. Barnes, P. J., C. T. Dollery, and J. MacDermot. Increased pulmonary α‐adrenergic and reduced β‐adrenergic receptors in experimental asthma. Nature London 285: 569–571, 1980.
 10. Barnes, P. J., P. W. Ind, and M. J. Brown. Plasma histamine and catecholamines in stable asthmatic subjects. Clin. Sci. 62: 661–665, 1982.
 11. Barnes, P. J., J. A. Nadel, J. M. Roberts, and C. B. Basbaum. Muscarinic receptors in lung and trachea: autoradiographic localization using [3H]quinuclidinyl benzilate. Eur. J. Pharmacol. 86: 103–106, 1982.
 12. Barnes, P. J., J. A. Nadel, B.‐E. Skoogh, and J. M. roberts. Characterization of beta‐adrenoceptor subtypes in canine airway smooth muscle by radioligand binding and physiological responses. J. Pharmacol. Exp. Ther. 225: 456–461, 1983.
 13. Barnes, P. J., B.‐E. Skoogh, J. K. Brown, and J. A. Nadel. Activation of α‐adrenergic response in tracheal smooth muscle: a postreceptor mechanism. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 54: 1469–1476, 1983.
 14. Barnes, P. J., B.‐E. Skoogh, J. A. Nadel, and J. M. Roberts. Postsynaptic alpha2‐adrenoceptors predominate over alpha1‐adrenoceptors in canine tracheal smooth muscle and mediate neuronal and hormonal alpha‐adrenergic contraction. Mol. Pharmacol. 23: 570–575, 1983.
 15. Barnes, P. J., N. M. Wilson, and H. Vickers. Prazosin, an alpha1‐adrenoreceptor antagonist, partially inhibits exercise‐induced asthma. J. Allergy Clin. Immunol. 68: 411–415, 1981.
 16. Baum, T., and A. T. Shropshire. Influence of prostaglandins on autonomic responses. Am. J. Physiol. 221: 1470–1475, 1971.
 17. Benoy, C. J., M. S. El‐Fellah, R. Schneider, and O. L. Wade. Tolerance to sympathomimetic bronchodilators in guinea‐pig isolated lungs following chronic administration in vivo. Br. J. Pharmacol. 55: 547–554, 1975.
 18. Biel, M., and M. A. deKock. Role of alpha‐adrenergic receptors in exercise‐induced bronchoconstriction. Respiration 35: 78–86, 1978.
 19. Black, J., A. Turner, and J. Shaw. α‐Adrenoceptors in human peripheral lung. Eur. J. Pharmacol. 72: 83–86, 1981.
 20. Boushey, H. A., and M. J. Holtzman. Autonomic regulation of airways: parasympathetic nervous system. In: Bronchial Asthma: Mechanisms and Therapeutics, edited by E. B. Weiss and M. S. Segal. Boston, MA: Little, Brown. In press.
 21. Boushey, H. A., M. J. Holtzman, J. R. Sheller, and J. A. Nadel. State of the art. Bronchial hyperreactivity. Am. Rev. Respir. Dis. 121: 389–413, 1980.
 22. Brooks, S. M., K. McGowan, I. L. Bernstein, P. Altenau, and J. peagler. Relationship between numbers of beta adrenergic receptors in lymphocytes and disease severity in asthma. J. Allergy Clin. Immunol. 63: 401–406, 1979.
 23. Brown, J. K., R. Shields, C. Jones, and W. M. Gold. Augmentation of α‐adrenergic contractions in the trachealis muscle of living dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 54: 1558–1566, 1983.
 24. Burnstock, G. Review lecture. Neurotransmitters and trophic factors in the autonomic nervous system. J. Physiol. London 313: 1–35, 1981.
 25. Cabezas, G. A., P. D. Graf, and J. A. Nadel. Sympathetic versus parasympathetic nervous regulation of airways in dogs. J. Appl. Physiol. 31: 651–655, 1971.
 26. Cavanaugh, M. J., and D. M. Cooper. Inhaled atropine sulfate: dose response characteristics. Am. Rev. Respir. Dis. 114: 517–524, 1976.
 27. Chamberlain, D. A., D. C. F. Muir, and K. P. Kennedy. Atropine methonitrate and isoprenaline in bronchial asthma. Lancet 2: 1019–1021, 1962.
 28. Chan‐Yeung, M. M. W., M. N. Vyas, and S. Grzybowski. Exercise‐induced asthma. Am. Rev. Respir. Dis. 104: 915–923, 1971.
 29. Chen, W. Y., A. M. Brenner, P. C. Weiser, and H. Chai. Atropine and exercise‐induced bronchoconstriction. Chest 79: 651–656, 1981.
 30. Chesrown, S. E., C. S. Venugopalan, W. M. Gold, and J. M. Drazen. In vivo demonstration of nonadrenergic inhibitory innervation of the guinea pig trachea. J. Clin. Invest. 65: 314–320, 1980.
 31. Coburn, R. F., and T. tomita. Evidence for nonadrenergic inhibitory nerves in the guinea pig trachealis muscle. Am. J. Physiol. 224: 1072–1080, 1973.
 32. Cockcroft, D. W., R. E. Ruffin, J. Dolovich, and F. E. Hargreave. Allergen‐induced increase in non‐allergic bronchial reactivity. Clin. Allergy 7: 503–513, 1977.
 33. Colebatch, H. J. H., and D. F. J. Halmagyi. Effect of vagotomy and vagal stimulation on lung mechanics and circulation. J. Appl. Physiol. 18: 881–887, 1963.
 34. Cookson, D. V., and C. E. Reed. A comparison of the effect of isoproterenol in the normal and asthmatic subject. Am. Rev. Respir. Dis. 88: 636–643, 1963.
 35. Copas, J. L., P. Borgeat, and P. J. Gardiner. The actions of 5‐, 12‐, and 15‐HETE on tracheobronchial smooth muscle. Prostaglandins Leukotrienes Med. 8: 105–114, 1982.
 36. Curry, J. J. Comparative action of acetyl‐beta‐methyl choline and histamine on the respiratory tract in normals, patients with hay fever, and subjects with bronchial asthma. J. Clin. Invest. 26: 430–438, 1947.
 37. Davis, C., and M. E. Connolly. Tachyphylaxis to beta‐adrenoceptor agonists in human bronchial smooth muscle: studies in vitro. Br. J. Clin. Pharmacol. 10: 417–423, 1980.
 38. Deal, E. C., Jr., E. R. McFadden, Jr., R. H. Ingram, Jr., and J. J. Jaeger. Hyperpnea and heat flux: initial reaction sequence in exercise‐induced asthma. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 46: 476–483, 1979.
 39. DeKock, M. A., J. A. Nadel, S. Zwi, H. J. H. Colebatch, and C. R. Olsen. New method for perfusing bronchial arteries: histamine bronchoconstriction and apnea. J. Appl. Physiol. 21: 185–194, 1966.
 40. Dey, R. D., W. A. Shannon, and S. I. Said. Localization of VIP‐immunoreactive nerves in airways and pulmonary vessels of dogs, cats, and human subjects. Cell Tissue Res. 220: 231–238, 1981.
 41. Drazen, J. M. Adrenergic influences on histamine‐mediated bronchoconstriction in the guinea pig. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 340–345, 1978.
 42. Empey, D. W., L. A. Laitinen, L. Jacobs, W. M. Gold, and J. A. Nadel. Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection. Am. Rev. Respir. Dis. 113: 131–139, 1976.
 43. Fleisch, J. H., and E. Titus. The prevention of isoproterenol desensitization and isoproterenol reversal. J. Pharmacol. Exp. Ther. 181: 425–433, 1972.
 44. Fraser, J., J. Nadeau, D. Robertson, and A. J. Wood. Regulation of human leukocyte beta receptors by endogenous catecholamines: relationship of leukocyte beta receptor density to the cardiac sensitivity to isoproterenol. J. Clin. Invest. 67: 1777–1784, 1981.
 45. Furchgott, R. F., T. D. Wakade, R. A. Sorace, and J. S. Stollak. Occurrence of both β1 and β2‐receptors in guinea‐pig tracheal smooth muscle, and variation of the β1:β2 ratio in different animals (Abstract). Federation Proc. 34: 794, 1975.
 46. Galant, S. P., L. Duriseti, S. Underwood, and P. A. Insel. Decreased beta‐adrenergic receptors on polymorphonuclear leukocytes after adrenergic therapy. N. Engl. J. Med. 299: 933–936, 1978.
 47. Ghatei, M. A., W. M. Sheppard, D. J. O'Shaughnessy, D. J. Adrian, T. E. McGregor, J. M. Polack, and S. R. Bloom. Regulatory peptides in the mammalian respiratory tract. Endocrinology 111: 1248–1254, 1982.
 48. Golden, J. A., J. A. Nadel, and H. A. Boushey. Bronchial hyperirritability in healthy subjects after exposure to ozone. Am. Rev. Respir. Dis. 118: 287–294, 1978.
 49. Goyal, R. K., S. Said, and S. Rattan. Influence of VIP antiserum on lower esophageal sphincter relaxation: possible evidence for VIP as the inhibitory neurotransmitter (Abstract). Gastroenterology 76: 1142, 1979.
 50. Griffin, M. P., K. F. Fung, R. H. Ingram, Jr., and E. R. McFadden, Jr. Dose‐response effects of atropine on thermal stimulus‐response relationships in asthma. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 53: 1576–1582, 1982.
 51. Grillo, M. A., and J. A. Nadel. Vital staining of tracheal ganglia (Abstract). Physiologist 23 (4): 77, 1980.
 52. Hahn, H. L., A. G. Wilson, P. D. Graf, S. P. Fischer, and J. A. Nadel. Interaction between serotonin and efferent vagus nerves in dog lungs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 144–149, 1978.
 53. Harvey, J. E., C. J. Baldwin, P. J. Wood, K. G. M. M. Alberti, and A. E. Tattersfield. Airway and metabolic responsiveness to intravenous salbutamol in asthma: effect of regular inhaled salbutamol. Clin. Sci. 60: 579–585, 1981.
 54. Henderson, W. R., J. H. Shelhamer, D. B. Reingold, L. J. Smith, R. Evans III, and M. Kaliner. Alpha‐adrenergic hyper‐responsiveness in asthma. Analysis of vascular and pupillary responses. N. Engl. J. Med. 300: 642–647, 1979.
 55. Herxheimer, H. Atropine cigarettes in asthma and emphysema. Br. Med. J. 2: 167–171, 1959.
 56. Holgate, S. T., C. J. Galdwin, and A. E. Tattersfield. Beta‐adrenergic agonist resistance in normal human airways. Lancet 2: 375–377, 1977.
 57. Holtzman, M. J., H. Aizawa, J. A. Nadel, and E. J. Goetzl. Selective generation of leukotriene B4 by tracheal epithelial cells from dogs. Biochem. Biophys. Res. Commun. 114: 1071–1076, 1983.
 58. Holtzman, M. J., J. H. Cunningham, J. R. Sheller, G. B. Irsigler, J. A. Nadel, and H. A. Boushey. Effect of ozone on bronchial reactivity in atopic and nonatopic subjects. Am. Rev. Respir. Dis. 120: 1059–1067, 1979.
 59. Holtzman, M. J., L. M. Fabbri, P. M. O'Byrne, B. D. Gold, H. Aizawa, E. H. Walters, S. E. Alpert, and J. A. Nadel. Importance of airway inflammation for hyperresponsiveness induced by ozone. Am. Rev. Respir. Dis. 127: 686–690, 1983.
 60. Holtzman, M. J., H. L. Hahn, K. Sasaki, B.‐E. Skoogh, P. D. Graf, L. M. Fabbri, and J. A. Nadel. Selective effect of general anesthetics on reflex bronchoconstrictor responses in dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 53: 126–133, 1982.
 61. Holtzman, M. J., J. R. Sheller, M. DiMeo, J. A. Nadel, and H. A. Boushey. Effect of ganglionic blockade on bronchial reactivity in atopic subjects. Am. Rev. Respir. Dis. 122: 17–25, 1980.
 62. Irvin, C. G., R. Boileau, J. Tremblay, R. R. Martin, and P. T. Macklem. Bronchodilatation: noncholinergic, nonadrenergic mediation demonstrated in vivo in the cat. Science 207: 791–792, 1980.
 63. Irvin, C. G., R. R. Martin, and P. T. Macklem. Nonpurinergic nature and efficacy of nonadrenergic bronchodilatation. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 562–569, 1982.
 64. Ito, Y., and K. Tajima. Spontaneous activity in the trachea of dogs treated with indomethacin: an experimental model for aspirin‐related asthma. Br. J. Pharmacol. 73: 563–571, 1981.
 65. Jenne, J. W., T. W. Chick, R. D. Strickland, and F. J. Wall. Subsensitivity of beta responses during therapy with a long‐acting beta‐2 preparation. J. Allergy Clin. Immunol. 59: 383–390, 1977.
 66. Kariman, K. β‐adrenergic receptor binding in lymphocytes from patients with asthma. Lung 158: 41–51, 1980.
 67. Kerr, J. W., M. Govindaraj, and K. R. Patel. Effect of alpha‐receptor blocking drugs and disodium cromoglycate on histamine hypersensitivity in bronchial asthma. Br. Med. J. 2: 139–141, 1970.
 68. Kitamura, S., Y. Ishihara, and S. I. Said. Effect of VIP, phenoxybenzamine and prednisolone on cyclic nucleotide content of isolated guinea‐pig lung and trachea. Eur. J. Pharmacol. 67: 219–223, 1980.
 69. Kneussl, M. P., and J. B. Richardson. Alpha‐adrenergic receptors in human and canine tracheal and bronchial smooth muscle. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 45: 307–311, 1978.
 70. Lackey, S. D., J. A. Glennon, and C. E. Reed. Comparison of some metabolic responses in normal and asthmatic subjects to epinephrine and glucagon. J. Allergy 40: 349–354, 1967.
 71. Lee, L.‐Y., E. R. Bleecker, and J. A. Nadel. Effect of ozone on bronchomotor response to inhaled histamine aerosol in dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 43: 626–631, 1977.
 72. Lee, L.‐Y., T. D. Djokic, C. Dumont, P. D. Graf, and J. A. Nadel. Mechanism of ozone‐induced tachypneic response to hypoxia and hypercapnia in conscious dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 48: 163–168, 1980.
 73. Lee, L.‐Y., C. Dumont, T. D. Djokic, T. E. Menzel, and J. A. Nadel. Mechanisms of rapid, shallow breathing after ozone exposure in conscious dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 46: 1108–1114, 1979.
 74. Leff, A., and N. M. Munoz. Interrelationship between alpha‐ and beta‐adrenergic agonists and histamine in canine airways. J. Allergy Clin. Immunol. 68: 300–309, 1981.
 75. Löfdahl, C.‐G., and N. Svedmyr. Effects of prenalterol in asthmatic patients. Eur. J. Clin. Pharmacol. 23: 297–302, 1982.
 76. Loring, S. H., J. M. Drazen, J. R. Snapper, and R. H. Ingram, Jr. Vagal and aerosol histamine interactions on airway responses in dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 45: 40–44, 1978.
 77. Lulich, K. M., H. W. Mitchell, and M. P. Sparrow. The cat lung strip as an in vitro preparation of peripheral airways: a comparison of beta‐adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea. Br. J. Pharmacol. 58: 71–79, 1976.
 78. Matsuzaki, Y., Y. Hamasaki, and S. I. Said. Vasoactive intestinal peptide: a possible transmitter of nonadrenergic relaxation of guinea pig airways. Science 210: 1252–1253, 1980.
 79. McNeill, R. S., and C. G. Ingram. Effect of propranolol on ventilatory function. Am. J. Cardiol. 18: 473–475, 1966.
 80. Middendorf, W. F., and J. A. Russell. Innervation of airway smooth muscle in the baboon: evidence for a nonadrenergic inhibitory system. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 48: 947–956, 1980.
 81. Murlas, C., J. A. Nadel, and J. M. Roberts. The muscarinic receptors of airway smooth muscle: their characterization in vitro. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 1084–1091, 1982.
 82. Nadel, J. A. Neurophysiology aspects of asthma. In: Asthma: Physiology, Immunopharmacology, and Treatment, edited by K. F. Austen and L. M. Lichtenstein. New York: Academic, 1973, p. 29–37.
 83. Nadel, J. A., H. Salem, B. Tamplin, and Y. Tokiwa. Mechanism of bronchoconstriction during inhalation of sulfur dioxide. J. Appl. Physiol. 20: 164–167, 1965.
 84. Nadel, J. A., and J. G. Widdicombe. Reflex effects of upper airway irritation on total lung resistance and blood pressure. J. Appl. Physiol. 17: 861–865, 1962.
 85. Nelson, H. S., J. W. Black, L. B. Branch, B. Pfuetze, H. Spaulding, R. Summers, and D. Wood. Subsensitivity to epinephrine following the administration of epinephrine and ephedrine to normal individuals. J. Allergy Clin. Immunol. 55: 299–309, 1975.
 86. O'Byrne, P., E. Walters, B. Gold, H. Aizawa, L. Fabbri, S. Alpert, J. Nadel, and M. Holtzman. Neutrophil depletion inhibits airway hyperresponsiveness induced by ozone (Abstract). Physiologist 26: 35, 1983.
 87. Olsen, C. R., H. J. H. Colebatch, P. E. Mebel, J. A. Nadel, and N. C. Staub. Motor control of pulmonary airways studied by nerve stimulation. J. Appl. Physiol. 20: 202–208, 1965.
 88. Orehek, J., J. S. Douglas, A. J. Lewis, and A. Bouhuys. Prostaglandin regulation of airway smooth muscle tone. Nature London New Biol. 245: 84–85, 1973.
 89. Orehek, J., P. Gayrard, C. Grimaud, and J. Charpin. Effect of beta‐adrenergic blockade on bronchial sensitivity to inhaled acetylcholine in normal subjects. J. Allergy Clin. Immunol. 55: 164–169, 1975.
 90. Partanen, M., A. Laitinen, A. Hervonen, M. Toivanen, and L. A. Laitinen. Catecholamine‐ and acetylcholinesterase‐containing nerves in human lower respiratory tract. Histochemistry 76: 175–188, 1982.
 91. Patel, K. R., J. W. Kerr, and J. B. MacDonald. The effect of thymoxamine and cromolyn sodium on postexercise bronchoconstriction in asthma. J. Allergy Clin. Immunol. 57: 285–292, 1976.
 92. Richardson, J., and J. Béland. Nonadrenergic inhibitory nervous system in human airways. J. Appl. Physiol. 41: 764–771, 1976.
 93. Richardson, J. B. State of the art. Nerve supply to the lungs. Am. Rev. Respir. Dis. 119: 785–802, 1979.
 94. Rinard, T. A., A. R. Rubinfeld, L. L. Brunton, and S. A. Mayer. Depressed cyclic AMP levels in airway smooth muscle from asthmatic dogs. Proc. Natl. Acad. Sci. USA 76: 1472–1476, 1980.
 95. Roberts, A. M., M. P. Kaufman, D. G. Baker, J. K. Brown, H. M. Coleridge, and J. C. G. Coleridge. Reflex tracheal contraction induced by stimulation of bronchial C‐fibers in dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 485–493, 1981.
 96. Russell, J. A., and S. Bartlett. Inhibition of adrenergic neurotransmission in airway smooth muscle by acetylcholine (Abstract). Federation Proc. 38: 1111, 1979.
 97. Sands, H. Effect of drug treatment and aerosoled antigen sensitization on cyclic AMP and β‐adrenergic receptors of guinea pig lung. Exp. Lung Res. 2: 1–8, 1981.
 98. Schreurs, A. J. M., and F. P. Nijkamp. Haemophilus influenzae induced loss of lung β‐adrenoceptor binding sites and modulation by changes in peripheral catecholaminergic input. Eur. J. Pharmacol. 77: 95–102, 1982.
 99. Severinghaus, J. W., and M. Stupfel. Respiratory dead space increase following atropine in man, and atropine, vagal or ganglionic blockade and hypothermia in dogs. J. Appl. Physiol. 8: 81–87, 1955.
 100. Sheller, J. R., M. J. Holtzman, B.‐E. Skoogh, and J. A. Nadel. Interaction of serotonin with vagal‐ and ACh‐induced bronchoconstriction in canine lungs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 964–966, 1982.
 101. Sheppard, D., W. S. Wong, C. F. Uehara, J. A. Nadel, and H. A. Boushey. Lower threshold and greater bronchomotor responsiveness of asthmatic subjects to sulfur dioxide. Am. Rev. Respir. Dis. 122: 873–878, 1980.
 102. Simonsson, B. G., F. M. Jacobs, and J. A. Nadel. Role of autonomic nervous system and the cough reflex in the increased responsiveness of airways in patients with obstructive airway disease. J. Clin. Invest. 46: 1812–1818, 1967.
 103. Simonsson, B. G., N. Svedmyr, B.‐E. Skoogh, R. Andersson, and N. P. Bergh. In vivo and in vitro studies on alpha‐receptors in human airways. Potentiation with bacterial endotoxin. Scand. J. Respir. Dis. 53: 227–236, 1972.
 104. Snashall, P. D., F. A. Boother, and G. M. Sterling. The effect of α‐adrenoreceptor stimulation on the airways of normal and asthmatic man. Clin. Sci. Mol. Med. 54: 283–289, 1978.
 105. Stephan, W. C., T. W. Chick, B. P. Avner, and J. W. Jenne. Tachyphylaxis to inhaled isoproterenol and the effect of methylprednisolone in dogs. J. Allergy Clin. Immunol. 65: 105–109, 1980.
 106. Szentivanyi, A. The β‐adrenergic theory of the atopic abnormality in bronchial asthma. J. Allergy 42: 203–232, 1968.
 107. Tam, E., D. Sheppard, J. Epstein, P. Ancic, and H. Boushey. Effect of increasing doses of ipratropium bromide on dose‐response curve to isocapnic hyperventilation with cold air in asthmatic subjects (Abstract). Am. Rev. Respir. Dis. 127: 250, 1983.
 108. Tashkin, D. P., M. E. Conolly, R. I. Deutsch, K. K. Hui, M. Littner, P. Scarpace, and I. Abrass. Subsensitization of beta‐adrenoceptors in airways and lymphocytes of healthy and asthmatic subjects. Am. Rev. Respir. Dis. 125: 185–193, 1982.
 109. Tattersfield, A. E., D. G. Leaver, and N. B. Pride. Effects of β‐adrenergic blockade and stimulation on normal human airways. J. Appl. Physiol. 35: 613–619, 1973.
 110. Thomson, N. C., E. E. Daniel, and F. E. Hargreave. Role of smooth muscle alpha1‐receptors in nonspecific bronchial responsiveness in asthma. Am. Rev. Respir. Dis. 126: 521–525, 1982.
 111. Townley, R. G., S. McGeady, and A. Bewtra. The effect of beta‐adrenergic blockade on bronchial sensitivity to acetyl‐beta‐methacholine in normal and allergic rhinitis subjects. J. Allergy Clin. Immunol. 57: 358–366, 1976.
 112. Vermeire, P. A., and P. M. Vanhoutte. Inhibitory effects of catecholamines in isolated canine bronchial smooth muscle. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 46: 787–791, 1979.
 113. Walters, E. H., P. M. O'Byrne, L. M. Fabbri, P. D. Graf, M. J. Holtzman, and J. A. Nadel. Control of neurotransmission by prostaglandins in canine trachealis smooth muscle. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 57: 129–134, 1984.
 114. Widdicombe, J. G. Action potentials in parasympathetic and sympathetic efferent fibres to the trachea and lungs of dogs and cats. J. Physiol. London 186: 56–88, 1966.
 115. Woolcock, A. J., P. T. Macklem, J. C. Hogg, and N. J. Wilson. Influence of autonomic nervous system on airway resistance and elastic recoil. J. Appl. Physiol. 26: 814–818, 1969.
 116. Yanta, M. A., S. H. Loring, R. H. Ingram, Jr., and J. M. Drazen. Direct and reflex bronchonconstriction induced by histamine aerosol inhalation in dogs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 50: 869–873, 1981.
 117. Yip, P., B. Palombini, and R. F. Coburn. Inhibitory innervation to the guinea pig trachealis muscle. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 50: 374–382, 1981.
 118. Zaid, G., and G. N. Beall. Bronchial response to beta‐adrenergic blockade. N. Engl. J. Med. 275: 580–584, 1966.

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Article Title: Autonomic Factors in Hyperreactivity of Airway Smooth Muscle
 

How to Cite

J. A. Nadel, P. J. Barnes, M. J. Holtzman. Autonomic Factors in Hyperreactivity of Airway Smooth Muscle. Compr Physiol 2011, Supplement 12: Handbook of Physiology, The Respiratory System, Mechanics of Breathing: 693-702. First published in print 1986. doi: 10.1002/cphy.cp030338