Comprehensive Physiology Wiley Online Library

Cardiovascular System

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Cardiovascular Structure in Younger and Older Humans
1.1 Arterial Structure and Mechanical Properties
1.2 Cardiac Structure
1.3 Ventricular–Vascular Coupling
2 Myocardial and Cardiac Pump Function at Rest
2.1 Integrated Regulation of Cardiac Function
2.2 Cardiac Filling (Diastolic) Properties
2.3 Cardiac Volumes and Ejection Fraction
2.4 Myocardial Contractile Properties
2.5 Heart Rate and Rhythm
2.6 Cardiac Output
3 Cardiovascular Reserve
3.1 Postural Reflexes
3.2 Isometric Exercise
3.3 Dynamic Exercise
4 Sympathetic Modulation of Cardiovascular Function
4.1 Intact Organisms
4.2 Cardiovascular Target Organ Response to β‐Adrenergic Stimulation with Aging
4.3 Isolated Tissue or Cells
5 Parasympathetic Modulation of Cardiovascular Function
6 Cardiovascular Structure and Function in Younger and Older Animals
6.1 Cardiac Structure
6.2 Myocardial Stiffness
6.3 Regulation of the Cardiac Contraction
6.4 Similar Effects of Aging and Experimental Pressure Overload on Cardiac Regulatory Mechanisms and Gene Expression
6.5 Possible Mechanisms of Altered Cardiac Gene Regulation with Aging
6.6 Response of Older Rat Heart to Chronic Hemodynamic Overload
6.7 Coronary Blood Flow, Oxygen Consumption, and Oxidative Metabolism
7 Effect of Chronic Physical Conditioning on Cardiovascular Performance in Older Humans and Animals
7.1 Studies in Humans
7.2 Studies in Rodents
8 Summary
Figure 1. Figure 1.

A: Mean brachial arterial aortic pressure and aortic pulse wave velocity in two Chinese populations selected without respect to arterial pressure (clinically hypertensive subjects included) and in a North American study population, the Baltimore Longitudinal Study of Aging (BLSA), in which hypertensive subjects (blood pressure greater than 140/90 mm Hg) were excluded from analysis . B: Augmentation index of the carotid artery pressure pulse in healthy individuals, measured in an applanation tonometry. The augmentation index is defined as the ratio of ΔP/PP%; ΔP is the pressure difference from the shoulder to peak; PP is pulse pressure. The ○ population included mildly hypertensive subjects.; the • population (BLSA) excluded clinically hypertensive subjects (blood pressure greater than 140/90 mm Hg). C: Hypothetical aortic input impedance spectra. Upper tracing, impedance modulus values decline from a high value at 0 Hz (the PVR) to a minimum at approximately 3.5 Hz. This is approximately the same frequency at which phase crosses zero (lower tracing). Negative phase values indicate that flow harmonics lead pressure harmonics; positive phase values indicate that flow harmonics lag pressure harmonics. Impedance moduli oscillate around a characteristic value (Z0 average of moduli > 2 Hz) because of wave reflections. A wave reflection index can be calculated as the difference between maximum and minimum impedance moduli. D: Aortic input impedance spectra and flow modulus vs. frequency in a young subject and an elderly subject. E: Characteristic aortic impedance increase with age.]

From Kelly et al. with permission; From Vaitkevicius et al. with permission; From Nichols et al. with permission; From Nichols et al. with permission; From Nichols et al. with permission;
Figure 2. Figure 2.

A: Least‐squares linear regression of left ventricular end‐diastolic wall thickness (LVWT) on age (solid line = mean; dashed lines = ± 2 standard deviations of the mean) in healthy men and women as measured by echocardiography. Circles indicate LVWT in patients with aortic valve disease. B: LVWT at end‐diastole (top) and at end‐systole (lower) measured via M‐mode echocardiography in healthy men participating in the BLSA.

From Sjögren with permission. From reference , with permission
Figure 3. Figure 3.

Arterial and cardiac changes that occur with aging in normotensive subjects and at any age in hypertensive subjects. One interpretation of the constellation (flow of arrows) is that vascular changes lead to cardiac structural and functional alterations that maintain cardiac function.

Modified from Lakatta with permission
Figure 4. Figure 4.

Multiple interdependent factors regulate cardiac output.

From Lakatta with permission
Figure 5. Figure 5.

A: Isovolumic relaxation time at rest measured from the closure of the aortic valve to the opening of the mitral valve in healthy male participants of the BLSA (Lakatta, E. G., and Fleg, J. L., unpublished results). B: Relationships between age and peak filling rate obtained at rest, at 50% of maximal workload, and at maximal workload. For each of these workloads, there was a significant inverse correlation between age and peak filling rate, r = −0.64 (rest), −0.53 (50% maximal workload), and −0.64 (maximal workload). The slopes of the three lines did not differ with a decrease in peak filling rate from 6% to 7% per decade .

Figure 6. Figure 6.

Linear regression on age of cardiac volume indices (A, at rest; B, during exercise) and ejection fraction (C), heart rate (D), cardiac index (E), systolic arterial pressure (F), and peripheral vascular resistance (G) at rest and during maximal cycle ergometry in the upright position. Study participants were healthy, sedentary male (n = 95, closed symbols) and female (n = 50, open symbols), community‐dwelling volunteers from the BLSA who had been rigorously screened to exclude clinical hypertension and occult coronary artery disease . Cardiac volumes were measured via gated blood‐pool scans . *Linear regression on age within sex is statistically significant. Age–gender interactions are described in Fleg et al. .

Figure 7. Figure 7.

Left ventricular SWI measured as the product of SVI and brachial systolic pressure at rest and during graded exercise in younger (< 40 yr) and older (> 60 yr) men (top), and women (bottom) of the study population depicted in Figure .

From Fleg et al. with permission
Figure 8. Figure 8.

A: Left ventricular contractility index (LVCTI) measured as the ratio of end‐systolic arterial pressure and ESVI. Lines are the best fit, linear regressions at rest and during exercise in the presence and absence of β‐adrenergic blockade with propranolol. B: The effect of exercise on characteristic aortic impedance during graded treadmill exercise in the presence and absence of β‐adrenergic blockade (propranolol) in healthy adult □ and senescent ▪ beagle dogs. In the absence of β‐adrenergic blockade, exercise increased impedance in senescent but not in younger dogs. In contrast, during β‐blockade impedance was increased during exercise in dogs of both ages.

From Fleg et al. with permission; From Yin et al. with permission
Figure 9. Figure 9.

O2max as a function of age as measured in males of varying age, fitness, and body composition. Points are average O2max values for groups of men of different ages from reports in the literature for young athletes, master athletes, lean untrained, and overweight untrained men . Champion young athletes, ○, Heath et al. and □ Dill et al. ; ex‐champion athletes, Δ, Dill et al. and Robinson et al. ; cross‐country runners, ▴, Grimby and Saltin ; runners ▪, Pollock et al. : groups of untrained men from 9 studies, • and X; master athletes ○ and •.

Modified from Heath et al. with permission; From Heath et al. and Fleg et al. , respectively, with permission
Figure 10. Figure 10.

A: The effect of a bolus I.V. isoproterenol infusion to increase heart rate in healthy young and older men at rest. B: Isoproterenol increases the LV ejection fraction in younger and older healthy men in the supine position prior to (pre) and following (post) chronic endurance training. Endurance training had no effect on this index of cardiac pump function or on its response to isoproterenol. C: Intraarterial isoproterenol (isoprenaline) infusions decrease the forearm vascular resistance in healthy younger and older men. D: I.V. arterial infusion of isoproterenol relaxes dorsal hand veins previously constricted by phenylephrine in men of varying ages. E: Top: Peak LV filling rates at rest and during exercise for young β‐blocked subjects and age‐matched non‐β‐blocked subjects. Peak filling rate was significantly less in those young subjects pretreated with propranolol at both relative and absolute workloads of 50% of maximal and maximal workloads (left) and 50 and 100 watts (right), respectively. Middle: Peak filling rates at rest and exercise for the older β‐blocked subjects and age‐matched non‐β‐blocked subjects. Peak filling rates were similar between the two groups both at relative workloads of 50% of maximal and maximal workloads (left) and absolute workloads of 50 and 100 watts (right). Lower: Peak filling rates at rest and exercise for young and old subjects pretreated with propranolol. Age differences noted during exercise in the absence of β‐blockade are no longer seen during exercise in the presence of β‐blockade.

From Yin et al. with permission; From Stratton et al. with permission; From van Brummelin et al. with permission; From Pan et al. with permission; From Schulman et al. with permission
Figure 11. Figure 11.

A: The effect of norepinephrine on the maximum rate of isometric tension development in isolated trabeculae from hearts of varying ages. B: Velocity of cell shortening and C maximum rate of increase of the Indo‐1 fluorescence transient, an index of sarcoplasmic reticulum Ca2+ release into the cytosol, during electrically stimulated twitch in single cardiac myocytes isolated from the hearts of rats of varying ages and loaded with the fluorescent probe Indo‐1. D: Norepinephrine increases the L‐type sarcolemmal channel current (Ica) measured via whole‐cell patch clamp technique in single cells isolated as in B and C. E: Norepinephrine increases phosphorylation of troponin I (TNI) in suspensions of heart cells isolated from hearts of rats of varying ages as in above panels. In B–E norepinephrine stimulated β‐receptors, because prazosin and α1‐AR antagonist had no effect on the results.

From Lakatta et al. with permission; From Xiao et al. with permission; From Xiao et al. with permission; From Sakai et al. with permission
Figure 12. Figure 12.

Simplified schematic of excitation–contraction coupling mechanisms in cardiac muscle. Ca2+ influx (ICa) via L‐type sarcolemmal Ca2+ channels, activated by depolarization during an action potential, triggers the release of Ca2+ from the sarcoplasmic reticulum to increase the cytosolic [Ca2+]. The binding of Ca2+ to troponin (TROP) enables actomyosin (AM) interaction, resulting in myofilament force production and shortening. Cytoplasmic [Ca2+] is then lowered and relaxation ensues (Mito, mitochondria).

Figure 13. Figure 13.

Action potential (A), isometric twitch (B), and Cai transient (C) measured via aequorin luminescence in isometric right ventricular papillar muscles isolated form the hearts of young adult and senescent Wistar rats. Inset in C indicates the time course of the Cai transient (trace 1) relative to that of the contraction (trace 2). D: The force–pCa relationship in cardiac muscle in which membranes have been destroyed by detergent (Triton X) treatment does not vary with age. E: The ability of left ventricular trabeculae carneae to respond, via a detectable twitch contraction, to paired stimulation decreases with age as the coupling interval of the paired stimuli decreases. F: Left ventricular cell volume (single cells isolated via collagenase digestion of hearts), measured via Coulter counter technique, increases with age.

A and B from Wei et al. ; C from Orchard and Lakatta with permission.; D From Bhatnagar et al. with permission; E From Lakatta et al. with permission; F From Fraticelli et al. with permission
Figure 14. Figure 14.

17.14. A: The effect of age on Ca2+ accumulation velocity by sarcoplasmic reticulum (SR) isolated from senescent and adult Wistar rat hearts. B: The effect of age on SR isolated from adult and senescent Fischer 344 rat hearts. Left, Vmax for Ca2+‐ATPase activity in isolated SR vesicles; middle, formation of phosphoenzyme product; right, concentration of SR Ca2+ pump protein. The effect of age on steady‐state mRNA levels for SR calsequestrin (D) Ca2+‐ATPase (C) in adult senescent Wistar rat hearts.

From Froehlich et al. with permission; From Tate et al. with permission; From Lompre et al. with permission
Figure 15. Figure 15.

A: Average values for α and β myosin heavy chain (MHC) mRNA/mRNA18S of individual Wistar rat hearts measured by dot blot analysis (n = 11, 6, 10, and 10 for ages 6 wk, 6, 18, and 24 months, respectively). B: The α and β MHC proteins (V1 and V3 isoforms) of hearts of the same rat strain. C: Ca2+‐activated myosin ATPase activity of Wistar rat hearts decreases with age. D: The velocity of shortening during lightly loaded isotonic contractions in isolated cardiac muscle from younger and older rats decreases with aging. E: Left ventricular actin isoforms (cardiac or skeletal) do not change with aging as do the MHC isoforms in the Wistar rat.

From O'Neill et al. with permission; From Effron et al. with permission; From Effron et al. with permission; From Capasso et al. with permission; From Carrier et al. with permission
Figure 16. Figure 16.

Chronic exercise training decreases the isometric contraction duration in isolated right ventricular papillary muscles of older Wistar rats (A) and the velocity of Ca2+ accumulation in sarcoplasmic reticulum isolated from Fischer 344 rats (B). In contrast, chronic exercise alters neither age‐associated decreases in the MHC isoform content (C) nor age‐associated changes in myosin ATPase activity (D).

A from Spurgeon et al. ; B and D from Tate et al. ; C from Farrar et al. with permission


Figure 1.

A: Mean brachial arterial aortic pressure and aortic pulse wave velocity in two Chinese populations selected without respect to arterial pressure (clinically hypertensive subjects included) and in a North American study population, the Baltimore Longitudinal Study of Aging (BLSA), in which hypertensive subjects (blood pressure greater than 140/90 mm Hg) were excluded from analysis . B: Augmentation index of the carotid artery pressure pulse in healthy individuals, measured in an applanation tonometry. The augmentation index is defined as the ratio of ΔP/PP%; ΔP is the pressure difference from the shoulder to peak; PP is pulse pressure. The ○ population included mildly hypertensive subjects.; the • population (BLSA) excluded clinically hypertensive subjects (blood pressure greater than 140/90 mm Hg). C: Hypothetical aortic input impedance spectra. Upper tracing, impedance modulus values decline from a high value at 0 Hz (the PVR) to a minimum at approximately 3.5 Hz. This is approximately the same frequency at which phase crosses zero (lower tracing). Negative phase values indicate that flow harmonics lead pressure harmonics; positive phase values indicate that flow harmonics lag pressure harmonics. Impedance moduli oscillate around a characteristic value (Z0 average of moduli > 2 Hz) because of wave reflections. A wave reflection index can be calculated as the difference between maximum and minimum impedance moduli. D: Aortic input impedance spectra and flow modulus vs. frequency in a young subject and an elderly subject. E: Characteristic aortic impedance increase with age.]

From Kelly et al. with permission; From Vaitkevicius et al. with permission; From Nichols et al. with permission; From Nichols et al. with permission; From Nichols et al. with permission;


Figure 2.

A: Least‐squares linear regression of left ventricular end‐diastolic wall thickness (LVWT) on age (solid line = mean; dashed lines = ± 2 standard deviations of the mean) in healthy men and women as measured by echocardiography. Circles indicate LVWT in patients with aortic valve disease. B: LVWT at end‐diastole (top) and at end‐systole (lower) measured via M‐mode echocardiography in healthy men participating in the BLSA.

From Sjögren with permission. From reference , with permission


Figure 3.

Arterial and cardiac changes that occur with aging in normotensive subjects and at any age in hypertensive subjects. One interpretation of the constellation (flow of arrows) is that vascular changes lead to cardiac structural and functional alterations that maintain cardiac function.

Modified from Lakatta with permission


Figure 4.

Multiple interdependent factors regulate cardiac output.

From Lakatta with permission


Figure 5.

A: Isovolumic relaxation time at rest measured from the closure of the aortic valve to the opening of the mitral valve in healthy male participants of the BLSA (Lakatta, E. G., and Fleg, J. L., unpublished results). B: Relationships between age and peak filling rate obtained at rest, at 50% of maximal workload, and at maximal workload. For each of these workloads, there was a significant inverse correlation between age and peak filling rate, r = −0.64 (rest), −0.53 (50% maximal workload), and −0.64 (maximal workload). The slopes of the three lines did not differ with a decrease in peak filling rate from 6% to 7% per decade .



Figure 6.

Linear regression on age of cardiac volume indices (A, at rest; B, during exercise) and ejection fraction (C), heart rate (D), cardiac index (E), systolic arterial pressure (F), and peripheral vascular resistance (G) at rest and during maximal cycle ergometry in the upright position. Study participants were healthy, sedentary male (n = 95, closed symbols) and female (n = 50, open symbols), community‐dwelling volunteers from the BLSA who had been rigorously screened to exclude clinical hypertension and occult coronary artery disease . Cardiac volumes were measured via gated blood‐pool scans . *Linear regression on age within sex is statistically significant. Age–gender interactions are described in Fleg et al. .



Figure 7.

Left ventricular SWI measured as the product of SVI and brachial systolic pressure at rest and during graded exercise in younger (< 40 yr) and older (> 60 yr) men (top), and women (bottom) of the study population depicted in Figure .

From Fleg et al. with permission


Figure 8.

A: Left ventricular contractility index (LVCTI) measured as the ratio of end‐systolic arterial pressure and ESVI. Lines are the best fit, linear regressions at rest and during exercise in the presence and absence of β‐adrenergic blockade with propranolol. B: The effect of exercise on characteristic aortic impedance during graded treadmill exercise in the presence and absence of β‐adrenergic blockade (propranolol) in healthy adult □ and senescent ▪ beagle dogs. In the absence of β‐adrenergic blockade, exercise increased impedance in senescent but not in younger dogs. In contrast, during β‐blockade impedance was increased during exercise in dogs of both ages.

From Fleg et al. with permission; From Yin et al. with permission


Figure 9.

O2max as a function of age as measured in males of varying age, fitness, and body composition. Points are average O2max values for groups of men of different ages from reports in the literature for young athletes, master athletes, lean untrained, and overweight untrained men . Champion young athletes, ○, Heath et al. and □ Dill et al. ; ex‐champion athletes, Δ, Dill et al. and Robinson et al. ; cross‐country runners, ▴, Grimby and Saltin ; runners ▪, Pollock et al. : groups of untrained men from 9 studies, • and X; master athletes ○ and •.

Modified from Heath et al. with permission; From Heath et al. and Fleg et al. , respectively, with permission


Figure 10.

A: The effect of a bolus I.V. isoproterenol infusion to increase heart rate in healthy young and older men at rest. B: Isoproterenol increases the LV ejection fraction in younger and older healthy men in the supine position prior to (pre) and following (post) chronic endurance training. Endurance training had no effect on this index of cardiac pump function or on its response to isoproterenol. C: Intraarterial isoproterenol (isoprenaline) infusions decrease the forearm vascular resistance in healthy younger and older men. D: I.V. arterial infusion of isoproterenol relaxes dorsal hand veins previously constricted by phenylephrine in men of varying ages. E: Top: Peak LV filling rates at rest and during exercise for young β‐blocked subjects and age‐matched non‐β‐blocked subjects. Peak filling rate was significantly less in those young subjects pretreated with propranolol at both relative and absolute workloads of 50% of maximal and maximal workloads (left) and 50 and 100 watts (right), respectively. Middle: Peak filling rates at rest and exercise for the older β‐blocked subjects and age‐matched non‐β‐blocked subjects. Peak filling rates were similar between the two groups both at relative workloads of 50% of maximal and maximal workloads (left) and absolute workloads of 50 and 100 watts (right). Lower: Peak filling rates at rest and exercise for young and old subjects pretreated with propranolol. Age differences noted during exercise in the absence of β‐blockade are no longer seen during exercise in the presence of β‐blockade.

From Yin et al. with permission; From Stratton et al. with permission; From van Brummelin et al. with permission; From Pan et al. with permission; From Schulman et al. with permission


Figure 11.

A: The effect of norepinephrine on the maximum rate of isometric tension development in isolated trabeculae from hearts of varying ages. B: Velocity of cell shortening and C maximum rate of increase of the Indo‐1 fluorescence transient, an index of sarcoplasmic reticulum Ca2+ release into the cytosol, during electrically stimulated twitch in single cardiac myocytes isolated from the hearts of rats of varying ages and loaded with the fluorescent probe Indo‐1. D: Norepinephrine increases the L‐type sarcolemmal channel current (Ica) measured via whole‐cell patch clamp technique in single cells isolated as in B and C. E: Norepinephrine increases phosphorylation of troponin I (TNI) in suspensions of heart cells isolated from hearts of rats of varying ages as in above panels. In B–E norepinephrine stimulated β‐receptors, because prazosin and α1‐AR antagonist had no effect on the results.

From Lakatta et al. with permission; From Xiao et al. with permission; From Xiao et al. with permission; From Sakai et al. with permission


Figure 12.

Simplified schematic of excitation–contraction coupling mechanisms in cardiac muscle. Ca2+ influx (ICa) via L‐type sarcolemmal Ca2+ channels, activated by depolarization during an action potential, triggers the release of Ca2+ from the sarcoplasmic reticulum to increase the cytosolic [Ca2+]. The binding of Ca2+ to troponin (TROP) enables actomyosin (AM) interaction, resulting in myofilament force production and shortening. Cytoplasmic [Ca2+] is then lowered and relaxation ensues (Mito, mitochondria).



Figure 13.

Action potential (A), isometric twitch (B), and Cai transient (C) measured via aequorin luminescence in isometric right ventricular papillar muscles isolated form the hearts of young adult and senescent Wistar rats. Inset in C indicates the time course of the Cai transient (trace 1) relative to that of the contraction (trace 2). D: The force–pCa relationship in cardiac muscle in which membranes have been destroyed by detergent (Triton X) treatment does not vary with age. E: The ability of left ventricular trabeculae carneae to respond, via a detectable twitch contraction, to paired stimulation decreases with age as the coupling interval of the paired stimuli decreases. F: Left ventricular cell volume (single cells isolated via collagenase digestion of hearts), measured via Coulter counter technique, increases with age.

A and B from Wei et al. ; C from Orchard and Lakatta with permission.; D From Bhatnagar et al. with permission; E From Lakatta et al. with permission; F From Fraticelli et al. with permission


Figure 14.

17.14. A: The effect of age on Ca2+ accumulation velocity by sarcoplasmic reticulum (SR) isolated from senescent and adult Wistar rat hearts. B: The effect of age on SR isolated from adult and senescent Fischer 344 rat hearts. Left, Vmax for Ca2+‐ATPase activity in isolated SR vesicles; middle, formation of phosphoenzyme product; right, concentration of SR Ca2+ pump protein. The effect of age on steady‐state mRNA levels for SR calsequestrin (D) Ca2+‐ATPase (C) in adult senescent Wistar rat hearts.

From Froehlich et al. with permission; From Tate et al. with permission; From Lompre et al. with permission


Figure 15.

A: Average values for α and β myosin heavy chain (MHC) mRNA/mRNA18S of individual Wistar rat hearts measured by dot blot analysis (n = 11, 6, 10, and 10 for ages 6 wk, 6, 18, and 24 months, respectively). B: The α and β MHC proteins (V1 and V3 isoforms) of hearts of the same rat strain. C: Ca2+‐activated myosin ATPase activity of Wistar rat hearts decreases with age. D: The velocity of shortening during lightly loaded isotonic contractions in isolated cardiac muscle from younger and older rats decreases with aging. E: Left ventricular actin isoforms (cardiac or skeletal) do not change with aging as do the MHC isoforms in the Wistar rat.

From O'Neill et al. with permission; From Effron et al. with permission; From Effron et al. with permission; From Capasso et al. with permission; From Carrier et al. with permission


Figure 16.

Chronic exercise training decreases the isometric contraction duration in isolated right ventricular papillary muscles of older Wistar rats (A) and the velocity of Ca2+ accumulation in sarcoplasmic reticulum isolated from Fischer 344 rats (B). In contrast, chronic exercise alters neither age‐associated decreases in the MHC isoform content (C) nor age‐associated changes in myosin ATPase activity (D).

A from Spurgeon et al. ; B and D from Tate et al. ; C from Farrar et al. with permission
References
 1. Aass, H., T. Skomedal, and J.‐B. Osnes. Increase of cyclic AMP in subcellular fractions of heart muscle after β‐adrenergic stimulation: prenalterol and isoprerialine caused different distribution of bound cyclic AMP. J. Mol. Cell. Cardiol. 20: 847–860, 1988.
 2. Abrass, I. B., and P. J. Scarpace. Human lymphocyte beta‐adrenergic receptors are unaltered with age. J. Gerontol. 36: 298–301, 1981.
 3. Abrass, I. B., and P. J. Scarpace. Catalytic unit of adenylate cyclase: reduced activity in aged‐human lymphocytes. J. Clin. Endocrinol. Metab. 55: 1026–1028, 1982.
 4. Abrass, I. B., J. L. Davis, and P. J. Scarpace. Isoproterenol responsiveness and myocardial β‐adrenergic receptors in young and old rats. J. Gerontol. 37: 156–160, 1982.
 5. Abu‐Erreish, G. M., J. R. Neely, J. T. Whitmer, V. Whitman, and D. R. Sanadi. Fatty acid oxidation by isolated perfused working hearts of aged rats. Am. J. Physiol. 232 (Endocrinol. Metab. Gastrointest. Physiol. 1): E258–E252, 1977.
 6. Adelstein, R. S., and E. Eisenberg. Regulation and kinetics of the actin‐myosin‐ATP interaction. Annu. Rev. Biochem. 49: 921–956, 1980.
 7. Afflitto, J. J., and M. A. Inchiosa, Jr.. Decrease in rat cardiac myosin ATPase with aortic constriction: prevention by thyroxine treatment. Life Sci. 25: 353–364, 1979.
 8. Alpert, N. R., and L. A. Mulieri. Increased myothermal economy of isometric force generation in compensated cardiac hypertrophy induced by pulmonary artery constriction in the rabbit. A characterization of heat liberation in normal and hypertrophied right ventricular papillary muscles. Circ. Res. 50: 491–500, 1982.
 9. Alpert, N. R., E. M. Blanchard, and L. A. Mulieri. The quantity and rate of Ca2+ uptake in normal and hypertrophied hearts. In: Pathophysiology of Heart Disease, edited by N. Dhalla, P. Singel, and R. E. Beamish. New York: Raven, 1983.
 10. Alpert, N. R., H. H. Gale, and N. Taylor. The effect of age on contractile protein ATPase activity and the velocity of shortening. In: Factors Influencing Myocardial Contractility, edited by R. D. Tanz, F. Kavaler, and J. Roberts. New York: Academic, 1967, p. 127–133.
 11. Alpert, N. R., L. A. Mulieri, and R. Z. Litten. Functional significance of altered myosin adenosine triphosphatase activity in enlarged hearts. Am. J. Cardiol. 44: 946–953, 1979.
 12. Altura, B. M., and B. T. Altura. Some physiological factors in vascular reactivity. I. Aging in vascular smooth muscle and its influence on reactivity. In: Factors Influencing Vascular Reactivity, edited by O. Carrier, Jr., and S. Shibata. Tokyo: Igaku‐Shoin, 1977, p. 169–188.
 13. Amery, A., H. Bossaert, and M. Verstraete. Muscle blood flow in normal and hypertensive subjects. Influence of age, exercise, and body position. Am. Heart J. 78: 211–216, 1969.
 14. Andersen, K. L., and L. Hermansen. Aerobic work capacity in middle‐aged Norwegian men. J. Appl. Physiol. 20: 432–436, 1965.
 15. Anversa, P., B. Hiler, R. Ricci, G. Guideri, and G. Olivetti. Myocyte cell loss and myocyte hypertrophy in the aging rat heart. J. Am. Coll. Cardiol. 8: 1441–1448, 1986.
 16. Anversa, P., T. Palackal, E. H. Sonnenblick, G. Olivetti, L. G. Meggs, and J. M. Capasso. Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Circ. Res. 67: 871–885, 1990.
 17. Anversa, P., E. Puntillo, P. Nikitin, G. Olivetti, J. M. Capasso, and E. H. Sonnenblick. Effects of age on mechanical and structural properties of myocardium of Fischer 344 rats. Am. J. Physiol. 256 (Heart Circ. Physiol. 25): H1440–H1449, 1989.
 18. Armstrong, P. W., T. P. Stopps, S. E. Ford, and A. J. De Bold. Rapid ventricular pacing in the dog: pathophysiologic studies of heart failure. Circulation 74: 1075–1084, 1986.
 19. Aronson, R. S. Afterpotentials and triggered activity in hypertrophied myocardium from rats with renal hypertension. Circ. Res. 48: 720–727, 1981.
 20. Arora, R. R., J. MaChac, M. E. Goldman, R. N. Butler, R. Gorlin, and S. F. Horowitz. Atrial kinetics and left ventricular diastolic filling in the healthy elderly. J. Am. Coll. Cardiol. 9: 1255–1260, 1987.
 21. Aschoff, L. Lectures in Pathology. New York: Paul Hoeber, 1924, p. 131.
 22. Asmussen, E. K. Fruensgaard, and S. Norgaard. A follow‐up longitudinal study of selected physiologic functions in former physical education students after forty years. J. Am. Geriatr. Soc. 23: 442–450, 1975.
 23. Astrand, I. Aerobic work capacity in men and women with special reference to age. Acta Physiol. Scand. Suppl. 169: 1–92, 1960.
 24. Astrand, I., P. O. Astrand, I. Hallback, and A. Kilbom. Reduction in maximal oxygen uptake with age. J. Appl. Physiol. 35: 649–654, 1973.
 25. Avolio, A. P., S. G. Chen, R. P. Wang, C. L. Zhang, M. F. Li, and M. F. O'Rourke. Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community. Circulation 68: 50–58, 1983.
 26. Avolio, A. P., K. M. Clyde, T. C. Beard, H. M. Cooke, K. K. Ho, and M. F. O'Rourke. Improved arterial distensibility in normotensive subjects on a low salt diet. Arteriosclerosis 6: 166–169, 1986.
 27. Avolio, A. P., F. Q. Deng, W. Q. Li, Y. F. Luo, Z. D. Huang, L. F. Xing, and M. F. O'Rourke. Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China. Circulation 71: 202–210, 1985.
 28. Ayobe, H. M., and R. C. Tarazi. Reversal of changes in myocardial β‐receptors and inotropic responsiveness with regression of cardiac hypertrophy in renal hypertensive rats (RHR). Circ. Res. 54: 125–134, 1984.
 29. Bader, H. Dependence of wall stress in the human thoracic aorta on age and pressure. Circ. Res. 20: 354–361, 1967.
 30. Bauters, C., J. M. Moalic, J. Bercovici, C. Mouas, R. Emanoil‐Ravier, S. Schiaffino, and B. Swynghedauw. Coronary flow as a determinant of c‐myc and c‐fos proto‐oncogene expression in an isolated adult rat heart. J. Mol. Cell. Cardiol. 20: 97–101, 1988.
 31. Becklake, M. R., H. Frank, G. R. Dagenais, G. L. Ostiguy, and C. A. Guzman. Influence of age and sex on exercise cardiac output. J. Appl. Physiol. 20: 938–947, 1965.
 32. Beer, M., S. Hacker, J. Poat, and S. M. Stahl. Independent regulation of β1 and β2‐adrenoceptors. Br. J. Pharmacol. 92: 827–834, 1987.
 33. Benestad, A. M. Trainability of old men. Acta Med. Scand. 178: 321–327, 1965.
 34. Benovic, J. L., M. Bouvier, M. G. Caron, and R. J. Lefkowitz. Regulation of adenylyl cyclase‐coupled β‐adrenergic receptors. Annu. Rev. Cell Biol. 4: 405–428, 1988.
 35. Bhan, A. K., and J. Scheuer. Effects of physical training on cardiac myosin ATPase activity. Am. J. Physiol. 228: 1178–1182, 1975.
 36. Bhatnagar, G. M., M. B. Effron, G. Ruano‐Arroyo, H. A. Spurgeon, and E. G. Lakatta. Dissociation of myosin Ca2+‐ATPase activity from myosin isoenzymes and conctractile function in rat myocardium [Abstract]. Fed. Proc. 44: 826, 1985.
 37. Bhatnagar, G. M., G. D. Walford, E. S. Beard, S. Humphreys, and E. G. Lakatta. ATPase activity and force production in myofibrils and twitch characteristics in intact muscle from neonatal, adult, and senescent rat myocardium. J. Mol. Coll. Cardiol. 16: 203–218, 1984.
 38. Bing, O. H. L., W. W. Brooks, C. H. Conrad, S. Sen, C. L. Perreault, and J. P. Morgan. Intracellular calcium transient in myocardium from spontaneously hypertensive rats during the transition to heart failure. Circ. Res. 68: 1390–1400, 1991.
 39. Binkhorst, R. A., J. Pool, P. Van Leeuwen, and A. Bouhuys. Maximum O2 uptake in healthy nonathletic males. Int. Z. Angew. Physiol. Einschl. Arbeitsphysiol. 22: 10–18, 1966.
 40. Boluyt, M. O., L. O'Neill, E. G. Lakatta, and M. T. Crow. Progressive elevation of atrial natriuretic factor mRNAs in rat heart with advancing age [Abstract]. J. Mol. Cell. Cardiol. 24 (Suppl. III): S.35, 1992.
 41. Boluyt, M. O., A. Younes, J. L. Caffrey, L. O'Neill, B. A. Barron, M. T. Crow, and E. G. Lakatta. Age‐associated increase in rat cardiac opioid production. Am. J. Physiol. 265: H212–H218, 1993.
 42. Boluyt, M. O., J. A. Opiteck, K. A. Esser, and T. P. White. Cardiac adaptations to aortic‐constriction in adult and aged rats. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H643–H648, 1989.
 43. Bonow, R. O., D. F. Vitale, S. L. Bacharach, B. J. Maron, and M. V. Green. Effects of aging on asynchronous left ventricular regional function and global ventricular filling in normal human subjets. J. Am. Coll. Cardiol. 11: 50–58, 1988.
 44. Borkan, G. A., D. E. Hults, S. G. Gerzof, A. H. Robbins, and C. K. Silbert. Age changes in body composition revealed by computed tomography. J. Gerontol. 38: 673–677, 1983.
 45. Bouthier, J. D., N. De Luca, M. E. Safar, and A. C. Simon. Cardiac hypertrophy and arterial distensibility in essential hypertension. Am. Heart J. 109: 1345–1352, 1985.
 46. Bramwell, J. C., and A. V. Hill. The velocity of the pulse wave in man. Proc. R. Soc. Lond. B Biol. Sci. 93: 298–306, 1922.
 47. Brandfonbrener, M., M. Landowne, and N. W. Shock. Changes in cardiac output with age. Circulation 12: 557–566, 1955.
 48. Bristow, M. R., R. E. Hershberger, J. D. Port, W. Minobe, and R. Rasmussen. Beta 1‐ and beta 2‐adrenergic receptor‐mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol. Pharmacol. 35: 295–303, 1989.
 49. Brodde, O.‐E., A. Daul, A. Wellstein, D. Palm, M. C. Michel, and J. J. Beckeringh. Differentiation in β1 ‐ and β2‐adrenoceptor‐mediated effects in humans. Am. J. Physiol. 254 (Heart Circ. Physiol. 23): H199–H206, 1988.
 50. Brodde, O.‐E., H‐R. Zerkowski, N. Doetsch, S. Motomura, M. Khamssi, and M. C. Michel. Myocardial beta‐adrenoceptor changes in heart failure: concomitant reduction in beta 1‐ and 2‐adrenoceptor function related to the degree of heart failure in patients with mitral valve disease. J. Am. Coll. Cardiol. 14: 323–331, 1989.
 51. Brown, A. M. Regulation of heartbeat by G protein‐coupled ion channels. Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H1621–H1628, 1990.
 52. Bruce, R. A., and T. R. Hornsten. Exercise stress testing in evaluation of patients with ischemic heart disease. Prog. Cardiovasc. Dis. 11: 371–390, 1969.
 53. Busby, D. E., and A. C. Burton. The effect of age on the elasticity of the major brain arteries. Can. J. Physiol. Pharmacol. 43: 185–202, 1965.
 54. Busby, M., E. A. Shefrin, and J. L. Fleg. Prevalence and long‐term significance of exercise‐induced frequent or repetitive ventricular ectopic beats in apparently healthy volunteers. J. Am. Coll. Cardiol. 14: 1659–1665, 1989.
 55. Buttrick, P., A. Malhotra, S. Factor, D. Greenen, L. Leinwand, and J. Scheuer. Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart. Circ. Res. 68: 645–652, 1991.
 56. Buxton, I. L. O., and L. L. Brunton. Action of the cardiac α1‐adrenergic receptor. Activation of cyclic AMP degradation. J. Biol. Chem. 260: 6733–6737, 1985.
 57. Buxton, I. L. O., and L. L. Brunton. Compartments of cyclic AMP and protein kinase in mammalian cardiomyoctes. J. Biol. Chem. 258: 10233–10239, 1983.
 58. Calderone, A., M. Bouvier, K. Li, C. Juneau, J. De Champlain, and J. L. Rouleau. Dysfunction of the beta‐ and alpha‐adrenergic systems in a model of congestive heart failure. The pacing‐overdrive dog. Circ. Res. 69: 332–343, 1991.
 59. Campbell, M. J., A. J. McComas, and F. Pettto. Physiological changes in ageing muscles. J. Neurol. Neurosurg. Psychiatry 36: 174–182, 1973.
 60. Capasso, J. M., A. Malhotra, R. M. Remily, J. Scheuer, and E. H. Sonnenblick. Effects of age on mechanical and electrical performance of rat myocardium. Am. J. Physiol. 245 (Heart Circ. Physiol. 14): H72–H81, 1983.
 61. Capasso, J. M., A. Malhotra, J. Scheuer, and E. H. Sonnenblick. Myocardial biochemical, contractile and electrical performance after imposition of hypertension in young and old rats. Circ. Res. 58: 445–460, 1986.
 62. Capasso, J. M., E. Puntillo, G. Olivetti, and P. Anversa. Differences in load dependence of relaxation between the left and right ventricular myocardium as a function of age in rats. Circ. Res. 65: 1499–1507, 1989.
 63. Carrier, L., K. R. Boheler, C. Chassagne, D. De La Bastie, C. Wisnewsky, E. G. Lakatta, and K. Schwartz. Expression of the sarcomeric actin isogenes in the rat heart with development and senescence. Circ. Res. 70: 999–1005, 1992.
 64. Carroll, J. D., S. Shroff, P. Wirth, M. Halsted, and S. I. Rajfer. Arterial mechanical properties in dilated cardiomyopathy. Aging and the response to nitroprusside. J. Clin. Invest. 87: 1002–1009, 1991.
 65. Carter, S. A. In vivo estimation of elastic characteristics of the arteries in the lower extremities of man. Can. J. Physiol. Pharmacol. 42: 309–413, 1964.
 66. Carter, W. J., W. F. Kelly, F. H. Faas, M. E. Lynch, and C. A. Perry. Effect of graded doses of tri‐iodothyronine on ventricular myosin ATPase activity and isomyosin profile in young and old rats. Biochem. J. 247: 329–334, 1987.
 67. Charlemagne, D., J.‐M. Maixent, M. Preteseille, and L. G. Lelievre. Ouabain binding sites and (Na+, K+)‐ATPase activity in rat cardiac hypertrophy. Expression of the neonatal forms. J. Biol. Chem. 261: 185–189, 1986.
 68. Chen, J. C., J. B. Wwarshaw, and D. R. Sanadi. Regulation of mitochondrial respiration in senescence. J. Cell. Physiol. 80: 141–148, 1972.
 69. Chesky, J. A., and M. Rockstein. Reduced myocardial actomyosin adenosine triphosphatase activity in the ageing male Fischer rat. Cardiovasc. Res. 11: 242–246, 1977.
 70. Chesky, J. A., S. Lafollette, M. Travis, and C. Fortado. Effects of physical training on myocardial enzyme activities in aging rats. J. Appl. Physiol. 55: 1349–1353, 1983.
 71. Chevalier, B., P. Mansier, F. Callens‐El Amrani, and B. Swynghedauw. β‐Adrenergic system is modified in compensatory pressure cardiac overload in rats: physiological and biochemical evidence. J. Cardiol. Pharmacol. 13: 412–420, 1989.
 72. Chevalier, B., P. Mansier, E. Teiger, F. Callens‐El Amrani, and B. Swynghedauw. Alterations in β adrenergic and muscarinic receptors in aged rat heart. Effects of chronic administration of propranolol and atropine. Mech. Ageing Dev. 60: 215–224, 1991.
 73. Chien, K. R., K. U. Knowlton, H. Zhu, and S. Chien. Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptative physiologic response. FASEB J. 5: 3037–3046, 1991.
 74. Chin, J. H., and B. B. Hoffman. Age‐related deficit in beta receptor stimulation of cAMP binding in blood vessels. Mech. Ageing Dev. 53: 111–125, 1990.
 75. Chou, H.‐T., Y. Yokota, and H. Fukuzaki. Left ventricular reserve of the hypertrophied heart in patients with systemic hypertension and hypertrophic cardiomyopathy—relation to age and left ventricular relative wall thickness. Jap. Circ. J. 54: 373–382, 1990.
 76. Clausen, J. P. Effects of physical conditioning. A hypothesis concerning circulatory adjustment to exercise. Scand. J. Clin. Lab. Invest. 24: 305–313, 1969.
 77. Cléroux, J., C. Giannattasio, G. Bolla, C. Cuspidi, G. Grassi, C. Mazzola, L. Sampieri, G. Seravalle, M. Valsecchi, and G. Mancia. Decreased cardiopulmonary reflexes with aging in normotensive humans. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H961–H968, 1989.
 78. Cliff, W. J. The aortic tunica media in aging rats. Exp. Mol. Pathol. 13: 172–189, 1970.
 79. Coggan, A., R. J. Spina, D. S. King, M. A. Rogers, M. Brown, and P. M. Nemeth. Skeletal muscle adaptations to endurance training in 60 to 70‐yr old men and women. J. Appl. Physiol. 72: 1780–1786, 1992.
 80. Coggan, A. R., R. J. Spina, M. A. Rogers, D. S. King, M. Brown, P. M. Nemeth, and J. O. Holloszy. Histochemical and enzymatic characteristics of skeletal muscle in master athletes. J. Appl. Physiol. 68: 1896–1901, 1990.
 81. Conway, J., R. Wheeler, and R. Sannerstedt. Sympathetic nervous activity during exercise in relation to age. Cardiovasc. Res. 5: 577–581, 1971.
 82. Cooper, G., IV., W. E. Mercer, J. K. Hoober, P. R. Gordon, R. L. Kent, I. K. Lauva, and T. A. Marino. Load regulation of the properties of adult feline cardiocytes. Role of substrate adhesion. Circ. Res. 58: 692–705, 1986.
 83. Cooper, T. G. Surgical sympathectomy and adrenergic function. Pharmacol. Rev. 18: 611–618, 1966.
 84. Corbin, J. D., P. H. Sugden, T. M. Lincoln, and S. L. Keely. Compartmentalization of adenosine 3′:5′‐monophosphate and adenosine 3′:5′‐monophosphate‐dependent protein kinase in heart tissues. J. Biol. Chem. 253: 3854–3861, 1977.
 85. Cournand, A., R. L. Riley, E. S. Breed, and E. Baldwin. Measurement of cardiac output in man using the technique of catheterization of the right auricle or ventricle. J. Clin. Invest. 24: 106–116, 1945.
 86. Craelius, W., V. Chen, and N. El‐Sherif. Stretch activated ion channels in ventricular myocytes. Biosci. Rep. 8: 407–414, 1988.
 87. Crawford, M. H., M. A. Petru, and C. Rabinowitz. Effect of isotonic exercise training on left ventricular volume during upright exercise. Circulation 72: 1237–1243, 1985.
 88. Curtis, B. M., and W. A. Catterall. Phosphorylation of the calcium antagonist receptor of the voltage‐sensitive calcium channel by cAMP‐dependent protein kinase. Proc. Natl. Acad. Sci. U.S.A. 82: 2528–2532, 1985.
 89. Dannenberg, A. L., D. Levy, and R. J. Garrison. Impact of age on echocardiographic left ventricular mass in a healthy population (the Framingham Study). Am. J. Cardiol. 64: 1066–1068, 1989.
 90. Danziger, R. S., M. Sakai, E. G. Lakatta, and R. G. Hansford. Interactive α‐ and β‐adrenergic actions of norepinephrine in rat cardiac myocytes. J. Mol. Cell. Cardiol. 22: 111–123, 1990.
 91. Danziger, R. S., J. D. Tobin, L. C. Becker, E. G. Lakatta, and J. L. Fleg. The age‐associated decline in glomerular filtration in healthy normotensive volunteers: lack of relationship to cardiovascular performance. J. Am. Geriatr. Soc. 38: 1127–1132, 1990.
 92. Davies, C. T. M. Limitations to the prediction of maximum O2 intake from cardiac frequency measurements. J. Appl. Physiol. 24: 700–706, 1968.
 93. Davies, H. E. F. Respiratory change in heart rate, sinus arrhythmia in the elderly. Gerontol. Clin. 17: 96–100, 1975.
 94. Day, M. L., D. Schwartz, R. C. Wiegand, P. T. Stockman, S. R. Brunnert, H. E. Tolunay, M. G. Currie, D. G. Standaert, and P. Needleman. Ventricular atriopeptin. Unmasking of messenger RNA and peptide synthesis by hypertrophy or dexamethasone. Hypertension 9: 485–491, 1987.
 95. de Garavilla, L., H. L. Valentine, J. S. Schenden, W. J. Kinnier, and R. C. Hanson. Age‐related cardiovascular effects of adenosine in guinea pigs. Drug Dev. Res. 28: 496–502, 1993.
 96. Dehn, M. M., and R. A. Bruce. Longitudinal variations in maximal oxygen intake with age and activity. J. Appl. Physiol. 33: 805–807, 1972.
 97. Deisher, T. A., S. Mankani, and B. B. Hoffman. Role of cyclic AMP‐dependent protein kinase in the diminished beta adrenergic responsiveness of vascular smooth muscle with increasing age. J. Pharmacol. Exp. Ther. 249: 812–819, 1989.
 98. De La Bastie, D., D. Levttsky, L. Rappaport, J. J. Mercadier, F. Marotte, C. Wisnewsky, V. Brovkovich, K. Schwartz, and A. M. Lompre. Function of the sarcoplasmic reticulum and expression of its Ca2+ ATPase gene in pressure overload‐induced cardiac hypertophy in the rat. Circ. Res. 66: 554–564, 1990.
 99. Delcayre, C., J. L. Samuel, F. Marotte, M. Best‐Belpomme, J. J. Mercadier, and L. Rappaport. Synthesis of stress proteins in rat cardiac myocytes 2–4 days after imposition of hemodynamic overload. J. Clin. Invest. 82: 460–468, 1988.
 100. Devereux, R. B., T. G. Pickering, M. H. Alderman, S. Chien, J. S. Borer, and J. H. Laragh. Left ventricular hypertrophy in hypertension. Prevalence and relationship to pathophysiologic variables. Hypertension 9: II‐53–11–60, 1987.
 101. Devries, H. A. Physiological effects of an exercise training regimen upon men aged 52 to 88. J. Gerontol. 25: 325–336, 1970.
 102. Dill, D. B., S. Robinson, and J. C. Ross. A longitudinal study of 16 champion runners. J. Sports Med. Phys. Fitness 7: 4–27, 1967.
 103. Dillmann, W. Influence of thyroid hormone administration on myosin ATPase activity and myosin isoenzyme distribution in the heart of diabetic rats. Metabolism 31: 199–204, 1981.
 104. Dillon, N., S. Chung, J. Kelly, and K. O'Malley. Age and beta adrenoceptor‐mediated function. Clin. Pharmacol. Ther. 27: 769–772, 1980.
 105. Dobson, J. G., Jr.. Mechanism of adenosine inhibition of catecholamine‐induced responses in heart. Circ. Res. 52: 151–160, 1983.
 106. Dobson, J. G., Jr., R. A. Fenton, and F. D. Romano. Increased myocardial adenosine production and reduction of β‐adrenergic contractile response in aged hearts. Circ. Res. 66: 1381–1390, 1990.
 107. Docherty, J. R., and L. Hyland. Aging and α‐adrenoceptor function. Trends Pharmacol. Sci. 7: 131–132, 1986.
 108. Docherty, J. R., and L. Hyland. Evidence for neuro‐effector transmission through postjunctional α2‐adrenoceptors in human saphenous vein. Br. J. Pharmacol. 84: 573–576, 1985.
 109. Docherty, J. R., A. MaCdonald, and J. C. McGrath. Further subclassification of α‐adrenoceptors in the cardiovascular system, vas deferens and anococcygeus of the rat. Br. J. Pharmacol. 67: 421–422, 1979.
 110. Dontas, A. S., H. C. Taylor, and A. Keys. Carotid pressure plethysmograms: effects of age, diastolic pressure, relative body weight, and physical activity. Archiv. Kreislaufforsch. 36: 49–58, 1961.
 111. Doyle, V., K. O'Malley, and J. G. Kelly. Human lymphocyte beta‐adrenoceptor density in relation to age and hypertension. J. Cardiovasc. Pharmacol. 4: 738–740, 1982.
 112. Dubell, W. H., M. R. Boyett, H. A. Spurgeon, A. Talo, M. D. Stern, and E. G. Lakatta. The cytosolic calcium transient modulates the action potential of rat ventricular myocytes. J. Physiol. 436: 347–369, 1991.
 113. Duckles, S. P. Age‐related changes in adrenergic neuronal function of rabbit vascular smooth muscle. Neurobiol. Aging 4: 151–156, 1983.
 114. Duckles, S. P., B. J. Carter, and C. L. Williams. Vascular adrenergic neuroeffector function does not decline in aged rats. Circ. Res. 56: 109–116, 1985.
 115. Ebert, T. J., C. V. Hughes, F. E. Tristani, J. A. Barney, and J. J. Smith. Effect of age and coronary heart disease on the circulatory responses to graded lower body negative pressure. Cardiovasc. Res. 16: 663–669, 1982.
 116. Ebert, T. J., B. J. Morgan, J. A. Barney, T. Denahan, and J. J. Smith. Effects of aging on baroreflex regulation of sympathetic activity in humans. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H798–H803, 1992.
 117. Ebrecht, G., H. Rupp, and R. Jacob. Alterations of mechanical parameters in chemically skinned preparations of rat myocardium as a function of isoenzyme pattern of myosin. Basic Res. Cardiol. 77: 220–234, 1982.
 118. Effron, M. B., G. M. Bhatnagar, H. A. Spurgeon, G. Ruano‐Arroyo, and E. G. Lakatta. Changes in myosin isoenzymes, ATPase activity, and contraction duration in rat cardiac muscle with aging can be modulated by thyroxine. Circ. Res. 60: 238–245, 1987.
 119. Eghbali, M., M. Eghbali, T. F. Robinson, S. Seifter, and O. O. Blumenfeld. Collagen accumulation in heart ventricles as a function of growth and aging. Cardiovasc. Res. 23: 723–729, 1989.
 120. Ehsani, A. A. Cardiovascular adaptations to exercise training in the elderly. Fed. Proc. 46: 1840–1843, 1987.
 121. Ehsani, A. A., T. Ogawa, T. R. Miller, R. J. Spina, and S. M. Jilka. Exercise training improves left ventricular systolic function in older men. Circulation 83: 96–103, 1991.
 122. Eichler, H. G., A. Hiremath, T. F. Blaschke, and B. B. Hoffman. Absence of age‐related changes in venous responsiveness to nitroglycerin in vivo in humans. Clin. Pharmacol. Ther. 42: 521–524, 1987.
 123. Elzinga, G., and N. Westerhof. Pressure and flow generated by the left ventricle against different impedances. Circ. Res. 32: 178–186, 1973.
 124. Engelmann, G. L., J. C. Vitullo, and R. G. Gerrity. Morphometric analysis of cardiac hypertrophy during development, maturation, and senescence in spontaneously hypertensive rats. Circ. Res. 60: 487–494, 1987.
 125. Ensor, R. E., J. L. Fleg, Y. C. Kim, E. F. de Leon, and S. M. Goldman. Longitudinal chest x‐ray changes in normal men. J. Gerontol. 38: 307–314, 1983.
 126. Ericsson, E., and L. Lundholm. Adrenergic β‐receptor activity and cyclic AMP metabolism in vascular smooth muscle; variations with age. Mech. Ageing Dev. 4: 1–6, 1975.
 127. Escande, D., D. Loisance, C. Planche, and E. Coraboeuf. Age‐related changes of action potential plateau shape in isolated human atrial fibers. Am. J. Physiol. 249 (Heart Circ. Physiol. 18): H843–H850, 1985.
 128. Esler, M., H. Skews, P. Leonard, G. Jackman, A. Bobok, and P. Korner. Age‐dependence of noradrenaline kinetics in normal subjects. Clin. Sci. 60: 217–219, 1981.
 129. Faber, M., and G. Moller‐Hou. The human aorta. V. Collagen and elastin in the normal and hypertensive aorta. Acta Pathol. Microbiol. Scand. 31: 377–382, 1952.
 130. Fagard, R., and J. Staessen. Relation of cardiac output at rest and during exercise to age in essential hypertension. Am. J. Cardiol. 67: 585–589, 1991.
 131. Fan, T. H., C. S. Liang, S. Kawashima, and S. P. Banerjee. Alterations in cardiac beta‐adrenoceptor responsiveness and adenylate cyclase system by congestive heart failure in dogs. Eur. J. Pharmacol. 140: 123–132, 1987.
 132. Farrar, R. P., J. W. Starnes, G. D. Cartee, P. Y. Oh, and H. L. Sweeney. Effects of exercise on cardiac myosin isozyme composition during the aging process. J. Appl. Physiol. 64: 880–883, 1988.
 133. Featherstone, J. A., R. C. Veith, D. Flatness, M. M. Murburg, E. C. Villacres, and J. B. Halter. Age and alpha‐2 adrenergic regulation of plasma norepinephrine kinetics in humans. J. Gerontol. 42: 271–276, 1987.
 134. Featherstone, J. A., R. C. Veith, and J. B. Halter. Effect of age and alpha‐2 adrenergic stimulation on plasma norepinephrine kinetics in man [Abstract]. Clin. Res. 32: 69A, 1984.
 135. Fein, F. S., L. B. Kornstein, J. E. Strobeck, J. M. Capasso, and E. H. Sonnenblick. Altered myocardial mechanics in diabetic rats. Circ. Res. 47: 922–933, 1980.
 136. Feldman, R. D., L. E. Limbird, J. Nadeau, D. Robertson, and A. J. Wood. Alterations in leukocyte beta‐receptor affinity with aging. A potential explanation for altered beta‐adrenergic sensitivity in the elderly. N. Engl. J. Med. 310: 815–819, 1984.
 137. Fenton, R. A., and J. G. Dobson, Jr.. Adenosine and calcium alter adrenergic‐induced intact heart protein phosphorylation. Am. J. Physiol. 246 (Heart Circ. Physiol. 15): H559–H565, 1984.
 138. Filburn, C. R., and E. G. Lakatta. Aging alterations in beta‐adrenergic modulation of cardiac cell function. In: Aging and Cell Function, edited by J. E. Johnson, Jr. New York: Plenum, 1984, p. 211–246.
 139. Fischer, A., J. Parizkova, and Z. Roth. The effect of systematic physical activity on maximal performance and functional capacity in senescent men. Int. Z. Angew. Physiol. Einschl. Arbeitsphysiol. 21: 269–304, 1965.
 140. Fitchett, D. H., G. J. Simkus, J. P. Beaudry, and D. G. F. Marpole. Reflected pressure waves in the ascending aorta: effect of glyceryl trinitrate. Cardiovasc. Res. 22: 494–500, 1988.
 141. Fleg, J. L., Arrhythmias and conduction disorders. In: The Merck Manual of Geriatrics, edited by W. B. Abrams and R. Berkow. Rahway, NJ: Merck Sharp & Dohme, 1990, p. 370–380.
 142. Fleg, J. L., and H. L. Kennedy. Cardiac arrhythmias in healthy elderly population: detection by 24‐hour ambulatory electrocardiography. Chest 81: 302–307, 1982.
 143. Fleg, J. L., and E. G. Lakatta. Role of muscle loss in the age‐associated reduction in VO2max. J. Appl. Physiol. 65: 1147–1151, 1988.
 144. Fleg, J. L., D. N. Das, J. Wright, and E. G. Lakatta. Age‐associated changes in the components of atrioventricular conduction in apparently healthy volunteers. J. Gerontol. Med. Sci. 45: M95–M100, 1990.
 145. Fleg, J. L., G. Gerstenblith, and E. G. Lakatta. Pathophysiology of the aging heart and circulation. In: Cardiovascular Disease in the Elderly (2nd ed.), edited by F. H. Messerli. Boston: Martinus Nijhoff, 1988, p. 9–35.
 146. Fleg, J., S. P. Schulman, G. Gerstenblith, L. C. Becker, F. C. O'Connor, and E. G. Lakatta. Additive effects of age and silent myocardial ischemia on the left ventricular response to upright cycle exercise. J. Appl. Physiol. 75: 499–504, 1993.
 147. Fleg, J. L., G. Gerstenblith, S. P. Schulman, L. C. Becker, F. C. O'Connor, and E. G. Lakatta. Gender differences in exercise hemodynamics of older subjects: effects of conditioning status [Abstract]. Circulation 82: III–239, 1990b.
 148. Fleg, J. L., G. Gerstenblith, A. B. Zonderman, L. C. Becker, M. L. Weisfeldt, P. T. Costa, Jr., and E. G. Lakatta. Prevalence and prognostic significance of exercise‐induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers. Circulation 81: 423–436, 1990c.
 149. Fleg, J. L., S. P. Schulman, F. C. O'Connor, G. Gerstenblith, L. C. Becker, S. Fortney, A. P. Goldberg, and E. G. Lakatta. Cardiovascular response to exhaustive upright cycle exercise in highly trained older men. J. Appl. Physiol. 77: 1500–1506, 1994.
 150. Fleg, J. L., S. Schulman, F. O'Connor, G. Gerstenblith, J. F. Clulow, D. G. Renlund, and E. G. Lakatta. Effect of propranolol on age‐associated changes in left ventricular performance during exercise [Abstract]. Circulation 84: 11–187, 1991.
 151. Fleg, J. L., E. Shapiro, F. O'Connor', L. Lakatta, and E. L. Lakatta. Failure of intensive aerobic conditioning to alter the age‐associated decline in diastolic left ventricular performance [Abstract]. Circulation 8 (suppl. I): 1–377, 1992.
 152. Fleg, J. L., S. P. Tzankoff, and E. G. Lakatta. Age‐related augmentation of plasma catecholamines during dynamic exercise in healthy males. J. Appl. Physiol. 59: 1033–1039, 1985.
 153. Fleisch, J. H. Age‐related decrease in beta adrenoreceptor activity of the cardiovascular system. Trends Pharmacol. Sci. 2: 337–339, 1981.
 154. Fleisch, J. H., and C. S. Hooker. The relationship between age and relaxation of vascular smooth muscle in the rabbit and rat. Circ. Res. 38: 243–249, 1976.
 155. Fleisch, J. H., H. M. Maling, and B. B. Brodie. Beta‐receptor activity in aorta; variations with age and species. Circ. Res. 26: 151–162, 1970.
 156. Ford, G. A., B. B. Hoffman, and T. F. Blaschke. Cardiac chronotropic and vascular smooth muscle beta adrenergic responses during propranolol therapy and withdrawal in young and elderly persons. J. Gerontol.: Med. Sci. 47: M22–M26, 1992.
 157. Forman, D. E., W. J. Manning, R. Hauser, E. V. Gervino, W. J. Evans, and J. Y. Wei. Enhanced left ventricular diastolic filling associated with long‐term endurance training. J. Gerontol.: Med. Sci. 47: M56–M58, 1992.
 158. Fortney, S., C. Tankersley, J. T. Lightfoot, D. Drinkwater, J. Clulow, F. O'Connor, L. Becker, E. Lakatta, and J. Fleg. Cardiovascular responses to lower body negative pressure in trained and untrained older men. J. Appl. Physiol. 73: 2693–2700, 1992.
 159. Fraticelli, A., R. Josephson, R. Danziger, E. Lakatta, and H. Spurgeon. Morphological and contractile characteristics of rat cardiac myocytes from maturation to senescence. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H259–H265, 1989.
 160. Freis, E. D., W. C. Heath, P. C. Luchsinger, and R. E. Snell. Changes in the carotid pulse which occur with age and hypertension. Am. Heart J. 71: 757–765, 1966.
 161. Frey, M. A. B., and G. W. Hoffler. Association of sex and age with responses to lower‐body negative pressure. J. Appl. Physiol. 65: 1752–1756, 1988.
 162. Friberg, P., M. Nordlander, S. Lundin, and B. Folkow. Effects of ageing on cardiac performance and coronary flow in spontaneously hypertensive and normotensive rats. Acta Physiol. Scand. 125: 1–11, 1985.
 163. Froehlich, J. P., E. G. Lakatta, E. Beard, H. A. Spurgeon, M. L. Weisfeldt, and G. Gerstenblith. Studies of sarcoplasmic reticulum function and contraction duration in young adult and aged rat myocardium. J. Mol. Cell Cardiol. 10: 427–438, 1978.
 164. Frolkis, V. V., V. V. Bezrukov, L. N. Bogatskaya, N. S. Verkhratsky, V. P. Zamostian, V. G. Shevtchuk, and I. V. Shtchegolva. Catecholamines in the metabolism and function regulation in aging. Gerontologia 16: 129–140, 1979.
 165. Frolkis, V. V., V. V. Bezrukov, and V. G. Schevtchuk. Hemodynamics and its regulation in old age. Exp. Gerontol. 10: 251–271, 1975.
 166. Frolkis, V. V., R. A. Frolkis, L. S. Mkhitarian, V. G. Schevchuk, V. E. Fraifeld, L. G. Vakulenko, and I. Syrovy. Contractile function and Ca2+ transport system of myocardium in ageing. Gerontology 34: 64–74, 1988.
 167. Frontera, W. R., C. N. Meredith, K. P. O'Reilly, and W. J. Evans. Strength training and determinants of VO2max in older men. J. Appl. Physiol. 68: 329–333, 1990.
 168. Frontera, W. R., C. N. Meredith, K. P. O'Reilly, H. G. Knuttgen, and W. J. Evans. Strength conditioning in older men: skeletal muscle hypertrophy and improved function. J. Appl. Physiol. 64: 1038–1044, 1988.
 169. Ganguly, P. K., G. N. Pierce, K. S. Dhalla, and N. S. Dhalla. Defective sarcoplasmic reticulum calcium transport in diabetic cardiomyopathy. Am. J. Physiol. 244 (Endocrinol. Metab. 7): E528–E535, 1983.
 170. Gardin, J. M., W. L. Henry, D. D. Savage, J. H. Ware, C. Burn, and J. S. Borer. Echocardiographic measurements in normal subjects: evaluation of an adult population without clinically apparent heart disease. J. Clin. Ultrasound 7: 439–447, 1979.
 171. Gende, O. A., A. Mattiazzi, M. C. Camillion, P. Pedroni, C. Taquini, H. Gomez‐Llami, and H. E. Cingolani. Renal hypertension impairs inotropic isoproterenol effect without β‐receptor changes. Am. J. Physiol. 249 (Heart Circ. Physiol. 18): H814–H819, 1985.
 172. Gerstenblith, G., J. Frederiksen, F. C. P. Yin, N. J. Fortuin, E. G. Lakatta, and M. L. Weisfeldt. Echocardiographic assessment of a normal adult aging population. Circulation 56: 273–278, 1977.
 173. Gerstenblith, G., E. G. Lakatta, and M. L. Weisfeldt. Age changes in myocardial function and exercise response. Prog. Cardiovasc. Dis. 19: 1–21, 1976.
 174. Gerstenblith, G., H. A. Spurgeon, J. P. Froehlich, M. L. Weisefeldt, and E. G. Lakatta. Diminished inotropic responsiveness to ouabain in aged rat myocardium. Circ. Res. 44: 517–523, 1979.
 175. Gey, K. P., W. P. Burkard, and A. Pletscher. Variation of the norepinephrine metabolism of the rat heart with age. In: Structure and Chemistry of the Aging Heart, edited by K. F. Gey, W. P. Burkard, V. V. Frolkis, et al. New York: MSS Information, 1974, p. 10–19.
 176. Gilman, A. G. G‐proteins: transducers of receptor‐generated signals. Annu. Rev. Biochem. 56: 615–649, 1987.
 177. Ginzton, L. E., R. Conant, M. Brizendine, and M. M. Laks. Effect of long‐term high intensity aerobic training on left ventricular volume during maximal upright exercise. J. Am. Coll. Cardiol. 14: 364–371, 1989.
 178. Godfraind, T. Alternative mechanisms for the potentiation of the relaxation evoked by isoprenaline in aortae from young and aged rats. Eur. J. Pharmacol. 53: 273–279, 1979.
 179. Goldstein, D. S., C. R. Lake, B. Chernow, M. G. Ziegler, M. D. Coleman, A. A. Taylor, J. R. Mitchell, I. J. Kopin, and H. R. Keiser. Age‐dependence of hypertensive‐normotensive differences in plasma norepinephrine. Hypertension 5: 100–104, 1983.
 180. Gozna, E. R., A. E. Marble, A. Shaw, and J. G. Holland. Age‐related changes in the mechanics of the aorta and pulmonary artery of man. J. Appl. Physiol. 36: 407–411, 1974.
 181. Granath, A., and T. Strandell. Relationships between cardiac output, stroke volume and intracardiac pressures at rest and during exercise in supine position and some anthropometric data in healthy old men. Acta Med. Scand. 176: 447–466, 1964.
 182. Granath, A., B. Jonsson, and T. Strandell. Circulation in healthy old men studied by right heart catheterization at rest and during exercise in supine and sitting position. Acta Med. Scand. 176: 425–446, 1964.
 183. Gribbin, B., T. G. Pickering, P. Sleight, and R. Peto. Effect of age and high blood pressure on baroreflex sensitivity in man. Circ. Res. 297: 424–431, 1971.
 184. Grimby, G., and B. Saltin. Physiological analysis of physically well‐trained middle‐aged and old athletes. Acta Med. Scand. 179: 513–526, 1966.
 185. Grimby, G., N. J. Nilsson, and B. Saltin. Cardiac output during submaximal and maximal exercise in active middle‐aged athletes. J. Appl. Physiol. 21: 1150–1156, 1966.
 186. Grobbee, D. E., and A. Hofman. Does sodium restriction lower blood pressure? Br. Med. J. Clin. Res. 293: 27–29, 1986.
 187. Guarnieri, T., C. R. Filburn, G. Zitnik, G. S. Roth, and E. G. Lakatta. Contractile and biochemical correlates of β‐adrenergic stimulation of the aged heart. Am. J. Physiol. 239 (Heart Circ. Physiol. 10): H501–H508, 1980.
 188. Guarnieri, T., H. Spurgeon, J. P. Froehlich, M. L. Weisfeldt, and E. G. Lakatta. Diminished inotropic response but unaltered toxicity to acetylstrophanthidin in the senescent beagle. Circulation 60: 1548–1554, 1979.
 189. Gwathmey, J. K., and J. P. Morgan. Altered calcium handling in experimental pressure‐overload hypertrophy in the ferret. Circ. Res. 57: 836–843, 1985.
 190. Gwathmey, J. K., M. T. Slawsky, C. L. Perreault, G. M. Briggs, J. P. Morgan, and J. Y. Wei. The effect of exercise conditioning on excitation‐contraction coupling in aged rats. J. Appl. Physiol. 69: 1366–1371, 1990.
 191. Haber, P., B. Honiger, M. Klicpera, and M. Niederberger. Effects in elderly people 67–76 years of age of three‐month endurance training on a bicycle ergometer. Eur. Heart J. 5 (suppl. E): 37–39, 1984.
 192. Hachamovitch, R., P. Wicker, J. M. Capasso, and P. Anversa. Alterations of coronary blood flow and reserve with aging in Fischer 344 rats. Am. J. Physiol. 256 (Heart Circ. Physiol. 27): H66–H73, 1989.
 193. Hagberg, J. M., W. K. Allen, D. R. Seals, B. F. Hurley, A. A. Ehsani, and J. O. Holloszy. A hemodynamic comparison of young and older endurance athletes during exercise. J. Appl. Physiol. 58: 2041–2046, 1985.
 194. Hagberg, J. M., J. E. Graves, M. Limacher, D. R. Woods, S. H. Leggett, C. Cononie, J. J. Gruber, and M. L. Pollock. Cardiovascular responses of 70‐ to 79‐yr‐old men and women to exercise training. J. Appl. Physiol. 66: 2589–2594, 1989.
 195. Hajduczok, G., M. W. Chapleau, and F. M. Abboud. Increase in sympathetic activity with age. II. Role of impairment of cardiopulmonary baroreflexes. Am. J. Physiol. 260 (Heart Circ. Physiol. 31): H1121–H1127, 1991.
 196. Hajduczok, G., M. W. Chapleau, S. L. Johnson, and F. M. Abboud. Increase in sympathetic activity with age. I. Role of impairment of arterial baroreflexes. Am. J. Physiol. 260 (Heart Circ. Physiol. 31): H1113–H1120, 1991.
 197. Hallock, P. and I. C. Benson. Studies on the elastic properties of human isolated aorta. J. Clin. Invest. 16: 595–602, 1937.
 198. Hammon, G. L., Y. K. Lai, and C. L. Markert. Diverse forms of stress lead to new patterns of gene expression through a common and essential metabolic pathway. Proc. Natl. Acad. Sci. U.S.A. 79: 3485–3488, 1982.
 199. Hanf, R., I. Drubaix, F. Marotte, and L. G. Lelievre. Rat cardiac hypertrophy. Altered sodium‐calcium exchange activity in sarcolemma vesicles. FEBS Lett. 236: 145–149, 1988.
 200. Hano, O., K. Y. Bogdanov, and E. G. Lakatta. Enhanced calcium intolerance manifest as aftercontractions and ventricular fibrillation in hearts of aged rats [Abstract]. J. Moll. Cell. Cardiol. 22: S.24, 1990.
 201. Hansford, R. G. Lipid oxidation by heart mitochondria from young adult and senescent rats. Biochem. J. 170: 285–295, 1978.
 202. Hansford, R. G., Metabolism and energy production. In: Aging: The Aging Heart: Its Function and Response to Stress, edited by M. L. Weisfeldt. New York: Raven, 1980, vol. 12, p. 25–76.
 203. Hanson, J. S., B. S. Tabakin, and A. M. Levy. Long‐term physical training and cardiovascular dynamics in middle‐aged men. Circulation 38: 783–799, 1968.
 204. Harding, S. E., S. M. Jones, P. O'Gara, F. Del Monte, G. Vescovo, and P. A. Poole‐Wilson. Isolated ventricular myocytes from failing and non failing human heart: the relation of age and clinical status of patients to isoproterenol response. J. Mol. Cell. Cardiol. 24: 549–564, 1992.
 205. Harrison, T. R., K. Dixon, P. O. Russell, Jr., P. S. Bidwai, and H. N. Coleman. The relation of age to the duration of contraction, ejection, and relaxation of the normal human heart. Am. Heart J. 67: 189–199, 1964.
 206. Hayes, J. S., L. L. Brunton, and S. E. Mayer. Selective activation of particulate cAMP‐dependent protein kinase by isoproterenol and prostaglandin E1. J. Biol. Chem. 255: 5113–5119, 1980.
 207. Haynes, F. W., L. B. Ellis, and S. Weiss. Pulse wave velocity and arterial elasticity in arterial hypertension, arteriosclerosis and related conditions. Am. Heart J. 11: 385–401, 1936.
 208. Heath, G. W., J. M. Hagberg, A. A. Ehsani, and J. O. Holloszy. A physiological comparison of young and older endurance athletes. J. Appl. Physiol. 51: 634–640, 1981.
 209. Heller, L. J. Augmented aftercontractions in papillary muscles from rats with cardiac hypertrophy. Am. J. Physiol. 237 (Heart Circ. Physiol. 8): H649–H654, 1979.
 210. Heller, L. J., and W. V. Whitehorn. Age‐associated alterations in myocardial contractile properties. Am. J. Physiol. 222: 1613–1619, 1972.
 211. Hellon, R. F., and A. R. Lind. The influence of age on peripheral vasodilatation in a hot environment. J. Physiol. (Lond.) 141: 262–272, 1958.
 212. Henry, P. D., G. G. Ahumada, W. F. Friedman, and B. E. Sobel. Simultaneously measured isometric tension and ATP hydrolysis in glycerinated fibers from normal and hypertrophied rabbit heart. Circ. Res. 31: 740–749, 1972.
 213. Heyliger, C. E., A. R. Prakash, and J. H. Mcneill. An assessment of phospholipid methylation in sarcolemma and sarcoplasmic reticulum of the aging myocardium. Biochim. Biophys. Acta 960: 462–465, 1988.
 214. Heyliger, C. E., A. R. Prakash, and J. H. Mcneill. Effect of calmodulin on sarcoplasmic reticular Ca2+‐transport in the aging heart. Mol. Cell. Biochem. 85: 75–79, 1989.
 215. Higginbotham, M. B., K. G. Morris, R. E. Coleman, and F. R. Cobb. Sex‐related differences in the normal cardiac response to upright exercise. Circulation 70: 357–366, 1984.
 216. Higginbotham, M. B., K. G. Morris, R. S. Williams, and F. R. Cobb. Physiologic basis for the age‐related decline in aerobic work capacity. Am. J. Cardiol. 57: 1374–1379, 1986.
 217. Higginbotham, M. B., K. G. Morris, R. S. Williams, P. A. McHale, R. E. Coleman, and F. R. Cobb. Regulation of stroke volume during submaximal and maximal upright exercise in normal man. Circ. Res. 58: 281–291, 1986.
 218. Hiremath, A. M., R. A. Pershe, B. B. Hoffman, and T. F. Blaschke. Comparison of age‐related changes in prostaglandin E1 and beta‐adrenergic responsiveness of vascular smooth muscle in adult males. J. Gerontol. Med. Sci. 44: M13–M17, 1989.
 219. Hoh, J. F. Y., and G. H. Rossmanith. Ventricular isomyosins and the tonic regulation of cardiac contractility. In: Pathobiology of Cardiovascular Injury, edited by H. L. Stone and W. B. Weglicki. Boston: Martinus Nijhoff, 1985.
 220. Hoh, J. F. Y., P. A. Mcgrath, and P. T. Hale. Electrophoretic analysis of multiple forms of rat cardiac myosin: effects of hypophysectomy and thyroxine replacement. J. Mol. Cell. Cardiol. 10: 1053–1076, 1978.
 221. Hosey, M. M., M. Borsotto, and M. Lazdunski. Phosphorylation and dephosphorylation of dihydropyridine‐sensitive voltage‐dependent Ca2+ channel in skeletal muscle membranes by cAMP‐ and CA2+‐dependent processes. Proc. Natl. Acad. Sci. U.S.A. 83: 3733–3737, 1986.
 222. Hossack, K. F., and R. A. Bruce. Maximal cardiac function in sedentary normal men and women: comparison of age‐related changes. J. Appl. Physiol. 53: 799–804, 1982.
 223. Houser, S. R., A. R. Freeman, J. M. Jaeger, E. A. Breisch, R. L. Coulson, R. Carey, and J. F. Spann. Resting potential changes associated with Na‐K pump in failing heart muscle. Am. J. Physiol. 240 (Heart Circ. Physiol. 11): H168–H176, 1981.
 224. Ikezono, K., H. R. Zerkowski, J. J. Beckeringh, M. C. Michel, and O. E. Brodde. Beta‐2 adrenoceptor‐mediated relaxation of the isolated human saphenous vein. J. Pharmacol. Exp. Ther. 241: 294–299, 1987.
 225. Isnard, R. N., B. M. Pannier, S. Laurent, G. M. London, B. Diebold, and M. E. Safar. Pulsatile diameter and elastic modulus of the aortic arch in essential hypertension: a noninvasive study. J. Am. Coll. Cardiol. 13: 399–405, 1989.
 226. Isoyama, S., W. Grossman, and J. Y. Wei. Effect of age on myocardial adaptation to volume overload in the rat. J. Clin. Invest. 81: 1850–1857, 1988.
 227. Izumo, S., B. Nadal‐Ginard, and V. Mahdavi. All members of the MHC multigene family respond to thyroid hormone in a highly tissue‐specific manner. Science 231: 597–600, 1986.
 228. Izumo, S., B. Nadal‐Ginard, and V. Mahdavi. Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc. Natl. Acad. Sci. U.S.A. 85: 339–343, 1988.
 229. Jacob, R., G. Kissling, G. Ebrecht, C. Holubarsch, I. Medugorac, and H. Rupp. Adaptive and pathological alterations in experimental cardiac hypertrophy. In: Advances in Myocardiology, edited by E. Chazov, V. Saks, and G. Rona. New York: Plenum, 1983, vol. 4., p. 55–77.
 230. Jansen, R. W., J. W. M. Lenders, T. Thien, and W. H. L. Hoefnagels. The influence of age and blood pressure on the hemodynamic and humoral response to head‐up tilt. J. Am. Geriatr. Soc. 37: 528–532, 1989.
 231. January, C. T., J. M. Riddle, and J. J. Salata. A model for early after‐depolarizations: induction with the Ca2+ channel agonist Bay K 8644. Circ. Res. 62: 563–571, 1988.
 232. Janz, R. F., B. R. Kubert, I. Mirsky, B. Korecky, and G. C. Taichman. Effect of age on passive elastic stiffness of rat heart muscle. Biophys. J. 16: 281–290, 1976.
 233. Jewell, B. R. A reexamination of the influence of muscle length on myocardial performance. Circ. Res. 40: 221–230, 1977.
 234. Jewell, B. R. Activation of contration in cardiac muscle. Mayo Clin. Proc. 57: 6–13, 1982.
 235. Jiang, M. T., and N. Naryanan. Effects of aging on phospholamban phosphorylation and calcium transport in rat cardiac sarcoplasmic reticulum. Mech. Ageing Dev. 54: 87–101, 1990.
 236. Joint National Committee. The 1984 report of the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure. Arch. Intern. Med. 144: 1045–1057, 1984.
 237. Jose, A. D. Effect of combined sympathetic and parasympathetic blockade on heart rate and cardiac function in man. Am. J. Cardiol. 18: 476–478, 1966.
 238. Julius, S., A. Amery, L. S. Whitlock, and J. Conway. Influence of age on the hemodynamic response to exercise. Circulation 36: 222–230, 1967.
 239. Kadoma, M., B. Sacktor, and J. P. Froehlich. Stimulation by cAMP and protein kinase of calcium transport in sarcoplasmic reticulum from senescent rat myocardium [Abstract]. Fed. Proc. 39: 2040, 1980.
 240. Kalish, M. I., M. S. Katz, M. A. Pineyro, and R. I. Gregerman. Epinephrine‐ and glucogon‐sensitive adenylate cyclases of rat liver during aging. Evidence for membrane instability associated with increased enzymatic activity. Biochim. Biophys. Acta 483: 452–466, 1977.
 241. Kane, R. L., T. A. Mcmahon, R. L. Wagner, and W. H. Abelmann. Ventricular elastic modulus as a function of age in the Syrian golden hamster. Circ. Res. 38: 74–80, 1976.
 242. Kannel, W. B., P. A. Wolf, D. L. McGee, T. R. Dawber, P. McNamara, and W. P. Castelli. Systolic blood pressure, arterial rigidity, and risk of stroke. The Framingham study. JAMA 245: 1225–1229, 1981.
 243. Kaplan, D., and K. Meyer. Mucopolysaccharides of aorta at various ages. Proc. Soc. Exp. Biol. Med. 105: 78–81, 1960.
 244. Karam, R., H. M. Lever, and B. P. Healy. Hypertensive hypertrophic cardiomyopathy or hypertrophic cardiomyopathy with hypertension? A study of 78 patients. J. Am. Coll. Cardiol. 13: 580–584, 1989.
 245. Kariya, K., L. R. Karns, and P. C. Simpson. Expression of a constitutively activated mutant of the β‐isozyme of protein kinase C in cardiac myocytes stimulates the promoter of the β‐myosin heavy chain isogene. J. Biol. Chem. 266: 10023–10026, 1991.
 246. Kassis, S., and P. H. Fishman. Functional alteration of the β‐adrenergic receptor during desensitization of mammalian adenylyl cyclase by β‐agonists. Proc. Natl. Acad. Sci. U.S.A. 81: 6686–6690, 1984.
 247. Kavanagh, T., and R. J. Shephard. The effects of continued training on the aging process. Ann. N.Y. Acad. Sci. 301: 656–670, 1977.
 248. Kawamoto, A., K. Shimada, K. Matsubayashi, T. Chikamori, O. Kuzume, H. Ogura, and T. Ozawa. Cardiovascular regulatory functions in elderly patients with hypertension. Hypertension 13: 401–407, 1989.
 249. Kelliher, G. J., and J. Conahan. Changes in vagal activity and response to muscarinic receptor agonists with age. J. Gerontol. 35: 842–849, 1980.
 250. Kelly, R., C. Hayward, A. Avolio, and M. O'Rourke. Noninvasive determination of age‐related changes in the human arterial pulse. Circulation 80: 1652–1659, 1989.
 251. Kelly, R. P., H. H. Gibbs, M. F. O'Rourke, J. E. Daley, K. Mang, J. J. Morgan, and A. P. Avolio. Nitroglycerin has more favourable effects on left ventricular afterload than apparent from measurement of pressure in a peripheral artery. Eur. Heart J. 11: 138–144, 1990.
 252. Kennedy, R. H., and E. Seifen. Aging: effects of chronotropic actions of muscarinic agonists in isolated rat atria. Mech. Ageing Dev. 51: 81–87, 1990.
 253. Kenney, W. L. Control of heat‐induced cutaneous vasodilatation in relation to age. Eur. J. Appl. Physiol. 57: 120–125, 1988.
 254. Kenney, W. L., C. G. Tankersley, D. L. Newswanger, D. E. Hyde, S. M. Puhl, and N. L. Turner. Age and hypohydration independently influence the peripheral vascular response to heat stress. J. Appl. Physiol. 68: 1902–1908, 1990.
 255. Kent, R. L., J. K. Hoober, and G. Cooper, IV.. Load responsiveness of protein synthesis in adult mammalian myocardium: role of cardiac deformation linked to sodium influx. Circ. Res. 64: 74–85, 1989.
 256. Khaw, K. T., and E. Barrett‐Cononr. The association between blood pressure, age, and dietary sodium and potassium: a population study. Circulation 77: 53–61, 1988.
 257. King, A. L. Pressure‐volume relation for cylindrical tubes with elastomeric walls: the human aorta. J. Appl. Physics 17: 501–505, 1946.
 258. Kino, M., V. Q. Lance, A. Shahamatpour, and D. H. Spodick. Effects of age on responses to isometric exercise. Isometric handgrip in noninvasive screening for cardiovascular disease. Am. Heart J. 90: 575–581, 1975.
 259. Kirchberger, M. A., E. Zhen, C. Kasinathan, and M. A. Kirchberger. Altered phospholamban phosphorylation in cardiac microsomes obtained from senescent rats [Abstract]. Biophys. J. 57: 504a, 1990.
 260. Kitzman, D. W., D. G. Scholz, P. T. Hagen, D. M. Ilstrup, and W. D. Edwards. Age‐related changes in normal human hearts during the first ten decades. Part II (Maturity): a quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. Mayo Clin. Proc. 63: 137–146, 1988.
 261. Kitzman, D. W., K. H. Sheikh, P. A. Beere, J. L. Philips, and M. B. Higginbotham. Age‐related alterations of Doppler left ventricular filling indexes in normal subjects are independent of left ventricular mass, heart rate, contractility and loading conditions. J. Am. Coll. Cardiol. 18: 1243–1250, 1991.
 262. Klein, C., W. R. Hiatt, J. G. Gerber, and A. S. Nies. Age does not alter human vascular and nonvascular β2‐adrenergic responses to isoproterenol. Clin. Pharmacol. Ther. 44: 573–578, 1988.
 263. Kobinger, W., α‐Adrenoceptors in cardiovascular regulation. In: Norepinephrine, edited by M. G. Ziegler and C. R. Lake. Baltimore: Williams and Wilkins, 1984, p. 307–326.
 264. Komuro, I., Y. Katoh, T. Kaida, Y. Shibazaki, M. Kurabayashi, E. Hoh Takaku, and Y. Yazaki. Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. Possible role of protein kinase C activation. J. Biol. Chem. 266: 1265–1268, 1991.
 265. Komuro, I., M. Kurabayashi, Y. Shibazaki, F. Takaku, and Y. Yazaki. Molecular cloning and characterization of a Ca2+ + Mg2+‐dependent adenosine triphosphatase from rat cardiac sarcoplasmic reticulum. Regulation of its expression by pressure overload and developmental stage. J. Clin. Invest. 83: 1102–1108, 1989.
 266. Korcky, B. The effects of load, internal environment and age on cardiac mechanics [Abstract]. J. Mol. Cell. Cardiol. 11 (suppl. 1): 33, 1979.
 267. Korkushko, O. V., V. B. Shatilo, and J. K. Kaukenas. Changes in heart rhythm power spectrum during human aging. Aging 3: 177–179, 1991.
 268. Kort, A. A, and E. G. Lakatta. Calcium‐dependent mechanical oscillations occur spontaneously in unstimulated mammalian cardiac tissues. Circ. Res. 54: 396–404, 1984.
 269. Kostis, J. B., A. E. Moreyra, M. T. Amendo, J. Di Pietro, N. Cosgrove, and P. T. Kuo. The effect of age on heart rate in subjects free of heart disease. Studies by ambulatory electrocardiography and maximal exercise stress test. Circulation 65: 141–145, 1982.
 270. Kraft, C. A., and C. M. Castleden. The effect of aging on β‐adrenoceptor‐stimulated cyclic AMP formation in human lymphocytes. Clin. Sci. 60: 587–589, 1981.
 271. Krall, J. F., M. Connelly, and M. L. Tuck. Evidence for reversibility of age‐related decrease in human lymphocyte adenylate cyclase activity. Biochem. Biophys. Res. Commun. 99: 1028–1034, 1981.
 272. Krall, J. F., M. Connelly, R. Weisbart, and M. L. Tuck. Age‐related elevation of plasma catecholamine concentration and reduced responsiveness of lymphocyte adenylate cyclase. J. Clin. Endocrinol. Metab. 52: 863–867, 1981.
 273. Kranz, D., and A. Wollenberger. Age dependence of adenylate cyclase activity and cAMP generation in aortas and femoral arteries of rats. Z. Alternsforsch. 32: 461–466, 1976.
 274. Kreider, M. S., P. B. Goldberg, and J. Roberts. Effect of age on adrenergic neuronal uptake in rat heart. J. Pharmacol. Exp. Ther. 231: 367–372, 1984.
 275. Kronenberg, R. S., and C. W. Drage. Attenuation of the ventilatory and heart rat responses to hypoxia and hypercapnia with aging in normal men. J. Clin. Invest. 52: 1812–1819, 1973.
 276. Kuecherer, H., K. Ruffmann, and W. Kuebler. Effect of aging on Doppler echocardiographic filling parameters in normal subjects and in patients with coronary artery disease. Clin. Cardiol. 11: 303–306, 1988.
 277. Kuickka, J. T., and E. Lansimies. Effect of age on cardiac index, stroke index and left ventricular ejection fraction at rest and during exercise as studied by radiocardiography. Acta Physiol. Scand. 114: 339–343, 1982.
 278. Kulchitskii, O. K. Effect of acetylcholine on the cyclic GMP level in the rat heart at different ages. Bull. Exp. Biol. Med. 90: 1237–1239, 1980.
 279. Kuo, L. C., M. A. Quinones, R. Rokey, M. Sartori, E. G. Abinader, and W. A. Zoghbi. Quantification of atrial contribution to left ventricular filling by pulsed Doppler echocardiography and the effect of age in normal and diseased hearts. Am. J. Cardiol. 59: 1174–1178, 1987.
 280. Kuramoto, K., S. Matsushita, J. Mifune, M. Sakai, and M. Murakami. Electrocardiographic and hemodynamic evaluations of isoproterenol test in elderly ischemic heart disease. Jpn. Circ. J. 42: 955–960, 1978.
 281. Kuroha, M., S. Isoyama, N. Ito, and T. Takishima. Effects of age on right ventricular hypertrophic response to pressure‐overload in rats. J. Mol. Cell. Cardiol. 23: 1177–1190, 1991.
 282. Kusiak, J. W., and J. Pitha. Decreased response with age of the cardiac catecholamine sensitive adenylate cyclase system. Life Sci. 33: 1679–1686, 1983.
 283. Lab, M. J. Contraction‐excitation feedback in myocardium. Physiological basis and clinical relevance. Circ. Res. 40: 757–766, 1982.
 284. Lagrue, G., J. C. Ansquer, and A. Meyer‐Heine. Peripheral action of spironolactone: improvement in arterial elasticity. Am. J. Cardiol. 65: 9K–11K, 1990.
 285. Lakatta, E. G. Determinants of cardiovascular performance: modification due to aging. J. Chron. Dis. 36: 15–30, 1983.
 286. Lakatta, E. G. Do hypertension and aging have a similar effect on the myocardium? Circulation 75 (suppl. I): 169–177, 1987.
 287. Lakatta, E. G. Chaotic behavior of myocardial cells: possible implications regarding the pathophysiology of heart failure. Perspect. Biol. Med. 32: 421–433, 1989.
 288. Lakatta, E. G., Normal changes of aging. In: Merck Manual of Geriatrics, edited by W. B. Abrarns and R. Berkow. Rahway, NJ: Merck Sharp & Dohme, 1990, p. 310–325.
 289. Lakatta, E. G., Regulation of cardiac muscle function in the hypertensive heart. In: Cellular and Molecular Mechanisms of Hypertension, edited by R. H. Cox. New York: Plenum, 1991, p. 149–173.
 290. Lakatta, E. G. Excitation–contration coupling in heart failure. Hosp. Pract. 26: 85–88, 1991.
 291. Lakatta, E. G., Length modulation of muscle performance: Frank‐Starling law of the heart. In: The Heart and Cardiovascular System (2nd ed.), edited by H. M. Fozzard, E. Haber, R. B. Jennings, A. M. Katz, and H. E. Morgan. New York: Raven, 1992, vol. 2, p. 1325–1351.
 292. Lakatta, E. G., and D. L. Lappe. Diastolic scattered light fluctuation, resting force and twitch force in mammalian cardiac muscle. J. Physiol. (Lond.) 315: 369–394, 1981.
 293. Lakatta, E. G., and W. L. Maughan. Cardiovascular function. In: Current Concepts in Cardiovascular Physiology, edited by O. B. Garfein. New York: Academic Press, 1990, p. 351–464.
 294. Lakatta, E. G., and F. C. P. Yin. Myocardial aging: functional alterations and related cellular mechanisms. Am. J. Physiol. 242 (Heart Circ. Physiol. 13): H927–H941, 1982.
 295. Lakatta, E. G., G. Gerstenblith, C. S. Angell, N. W. Shock, and M. L. Weisfeldt. Diminished inotropic response of aged myocardium to catecholamines. Circ. Res. 36: 262–269, 1975a.
 296. Lakatta, E. G., G. Gerstenblith, C. S. Angell, N. W. Shock, and M. L. Weisfeldt. Prolonged contraction duration in aged myocardium. J. Clin. Invest. 55: 61–68, 1975b.
 297. Lakatta, E. G., H. J. Mitchell, A. Pomerance, and G. G. Rowe. Human aging: changes in structure and function. J. Am. Coll. Cardiol. 10: 42A–47A, 1987.
 298. Lakatta, E. G., F. O'Connor, S. Schulman, G. Gerstenblith, L. Becker, and J. L. Fleg. Cardiac volumes at rest and during cycle exercise in healthy men of a broad age range: effect of fitness matching [Abstract]. FASEB J. 5: A766, 1991.
 299. Lamers, J. M. J., and J. T. Stinis. Defective calcium pump in the sarcoplasmic reticulum of the hypertrophied rabbit heart. Life Sci. 24: 2313–2319, 1979.
 300. Lamonica, D. A., N. Frohloff, and J. G. Dobson, Jr.. Adenosine inhibition of catecholamine‐stimulated cardiac membrane adenylate cyclase. Am. J. Physiol. 248 (Heart Circ. Physiol. 19): H737–H744, 1985.
 301. Landowne, M. The relation between intra‐arterial pressure and impact pulse wave velocity with regard to age and arteriosclerosis. J. Gerontol. 13: 153–161, 1958.
 302. Langer, S. Z. The role of α‐ and β‐presynaptic receptors in the regulation of noradrenaline release elicited by nerve stimulation. Clin. Sci. Mol. Med. 51 (suppl. 3): 423s–426s, 1976.
 303. Lansing, A. I. The Arterial Wall: Aging, Structure, and Chemistry. Baltimore: Williams and Wilkins, 1959, p. 136–160.
 304. Learoyd, B. M., and M. G. Taylor. Alterations with age in the viscoelastic properties of human arterial walls. Circ. Res. 18: 278–292, 1966.
 305. Le Blac, P. R., and K. Rakusan. Effects of age and isoproterenol on the cardiac output and regional blood flow in the rat. Can. J. Cardiol. 3: 246–250, 1987.
 306. Lecarpentier, Y., L. B. Bugaisky, D. Chemla, J. J. Mercadier, K. Schwartz, R. G. Whalen, and J. L. Martin. Coordinated changes in contractility, energetics, and isomyosins after aortic stenosis. Am. J. Physiol. 252 (Heart Circ. Physiol. 23): H275–H282, 1987.
 307. Lecarpentier, Y., A. Waldenstrom, M. Clerque, D. Chemla, P. Oliviero, J. L. Martin, and B. Swynghedauw. Major alterations in relaxation during cardiac hypertrophy induced by aortic stenosis in guinea pig. Circ. Res. 61: 107–116, 1987.
 308. Lee, J. C., L. M. Karpeles, and S. E. Downing. Age‐related changes of cardiac performance in male rats. Am. J. Physiol. 222: 432–438, 1972.
 309. Lefkowitz, R. J., W. P. Hausdorff, and M. G. Caron. Role of phosphorylation in desensitization of the β‐adrenoceptor. Trends Pharmacol. Sci. 11: 190–194, 1990.
 310. Lehmann, M., P. Schmid, and J. Keul. Age‐ and exercise‐related sympathetic activity in untrained volunteers, trained athletes and patients with impaired left‐ventricular contractility. Eur. Heart J. 5 (suppl. E): 1–7, 1984.
 311. Levitzki, A. Regulation of hormone‐sensitive adenylate cyclase. Trends Pharmacol. Sci. 8: 299–303, 1987.
 312. Lewis, W. H. Changes with age in the cardiac output of adult men. Am. J. Physiol. 121: 517–527, 1938.
 313. Lexell, J., K. Henriksson‐Larsen, B. Winblad, and M. Sjöström. Distribution of different fiber types in human skeletal muscles: effects of aging studied in whole muscle cross sections. Muscle Nerve 6: 588–595, 1983.
 314. Lexell, J., C. C. Taylor, and M. Sjöström. What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15‐ to 83‐year‐old men. J. Neurol. Sci. 84: 275–294, 1988.
 315. Li, Y. X., T. Lincoln, D. Mendelowitz, W. Grossman, and J. Y. Wei. Age‐related differences in effect of exercise training on cardiac muscle function in rats. Am. J. Physiol. 251 (Heart Circ. Physiol. 22): H12–H18, 1986.
 316. Lindeman, R. D., and R. Goldman. Anatomic and physiologic age changes in the kidney. Exp. Gerontol. 21: 379–406, 1986.
 317. Linzbach, A. J., and E. Akuamoa‐Boateng. Die alternsveranderungen des menschlichen herzens I. Das herzgewicht in alter. Klin. Wochenschr. 51: 156–163, 1973.
 318. Lipsitz, L. A. Orthostatic hypotension in the elderly. N. Engl. J. Med. 321: 952–957, 1989.
 319. Litsitz, L. A., P. V. Jonsson, B. L. Marks, J. A. Parker, J. D. Royal, and J. Y. Wei. Reduced supine cardiac volumes and diastolic filling rates in elderly patients with chronic medical conditions. J. Am. Geriatr. Soc. 38: 103–107, 1990.
 320. Lohse, M. J., J. L. Benovic, J. Codina, M. G. Caron, and R. J. Lefkowitz. Barrestin—a novel protein that regulates β‐adrenergic‐receptor function [Abstract]. Circulation 82 (suppl. III): III–L, 1990.
 321. Lompres, A. M., F. Lambert, E. G. Lakatta, and K. Schwartz. Expression of sarcoplasmic reticulum Ca2+‐ATPase and calsequestrin genes in rat heart during ontogenic development and aging. Circ. Res. 69: 1380–1388, 1991.
 322. Lompre, A. M., K. Schwartz, A. d'Albis, G. Lacombe, N. Van Thiem, and B. Swynghedauw. Myosin isozyme redistribution in chronic heart overload. Nature 282: 105–107, 1979.
 323. London, G. M., M. E. Safar, Y. A. Weiss, and P. L. Milliez. Isoproterenol sensitivity and total body clearance of propranolol in hypertensive patients. J. Clin. Pharmacol. 16: 174–183, 1976.
 324. Lopaschuk, G. D., A. G. Tahiliani, R. V. S. V. Vadlamudi, S. Katz, and J. H. McNeill. Cardiac sarcoplasmic reticulum function in insulin‐ or carnitine‐treated diabetic rats. Am. J. Physiol. 245 (Heart Circ. Physiol. 16): H969–H976, 1983.
 325. Luisada, A. A., K. Watanabe, P. K. Bhat, D. B. Rao, and V. Knighten. Correlates of the echocardiographic waves of the mitral valve in normal subjects of various ages. J. Am. Geriatr. Soc. 23: 216–223, 1975.
 326. Lund‐Johansen, L. Twenty‐year follow‐up of hemodynamics in essential hypertension during rest and exercise. Hypertension 18: 11154–11161, 1991.
 327. Lye, M., and E. Vargas. An analysis of impedance cardiography in the elderly. J. Med. Eng. Technol. 5: 289–292, 1981.
 328. Maciel, L. M. Z., R. Polikar, D. Rohrer, B. K. Popovich, and W. V. Dillmann. Age‐induced decreases in the messenger RNA coding for the sarcoplasmic reticulum Ca2+‐ATPase of the rat heart. Circ. Res. 67: 230–234, 1990.
 329. Maclennan, W. J., M. R. P. Hall, and J. I. Timothy. Postural hypotension in old age: is it a disorder of the nervous system or of blood vessels? Age Ageing 9: 25–32, 1980.
 330. Malhotra, A., S. Penpargkul, F. S. Fein, E. H. Sonnenblick, and J. Scheuer. The effect of streptozotocin‐induced diabetes in rats on cardiac contractile proteins. Circ. Res. 49: 1243–1250, 1981.
 331. Mann, D. L., B. S. Denenberg, A. K. Gash, P. T. Makler, and A. A. Bove. Effects of age on ventricular performance during graded supine exercise. Am. Heart J. 111: 108–115, 1986.
 332. Mann, D. L., R. L. Kent, and G. Cooper, IV.. Load regulation of the properties of adult feline cardiocytes: growth induction by cellular deformation. Circ. Res. 64: 1079–1090, 1989.
 333. Mansier, P., B. Chevalier, and B. Swynghedauw. Characterization of the beta adrenergic system in adult rat hypertrophied hearts [Abstract]. J. Mol. Cell. Cardiol. 21: S.17, 1989.
 334. Martin, C. E., J. A. Shaver, D. F. Leon, M. E. Thompson, P. S. Reddy, and J. J. Leonard. Autonomic mechanisms in hemodynamic responses to isometric exercise. J. Clin. Invest. 54: 104–115, 1974.
 335. Martin, W. H., III., E. F. Coyle, S. A. Bloomfield, and A. A. Ehsani. Effects of physical deconditioning after intense endurance training on left ventricular dimensions and stroke volume. J. Am. Coll. Cardiol. 7: 982–989, 1986.
 336. Martin, W. H., III, J. Montgomery, P. G. Snell, J. R. Corbett, J. J. Sokolov, J. C. Buckey, D. A. Maloney, and C. G. Blomqvist. Cardiovascular adaptations to intense swimming training in sedentary middle‐aged men and women. Circulation 75: 323–330, 1987.
 337. Marzo, K. P., M. J. Frey, J. R. Wilson, B. T. Liang, D. R. Manning, V. Lanoce, and P. B. Molinoff. Beta‐adrenergic receptor‐G protein‐adenylate cyclase complex in experimental canine congestive heart failure produced by rapid ventricular pacing. Circ. Res. 69: 1546–1556, 1991.
 338. Maughan, D., E. Low, R. Litten, III, J. Brayden, and N. Alpert. Calcium‐activated muscle from hypertophied rabbit hearts. Mechanical and correlated biochemical changes. Circ. Res. 44: 279–287, 1979.
 339. Mayoux, E., F. Callens, B. Swynghedauw, and D. Charlemagne. Adaptational process of the cardiac Ca2+ channels to pressure overload: biochemical and physiological properties of the dihydrophyridine receptors in normal and hypertrophied rat hearts. J. Cardiovasc. Pharmacol. 12: 390–396, 1988.
 340. Meerson, F. Z., M. P. Javich, and M. I. Lewrman. Decrease in the rate of RNA and protein synthesis and degradation in the myocardium under long‐term compensatory hyperfunction and on aging. J. Mol. Cell. Cardiol. 10: 145–159, 1978.
 341. Mercadier, J‐J., A.‐M. Lompre, C. Wisnewsky, J.‐L. Samuel, J. Bercovici, B. Swynghedauw, and K. Schwartz. Myosin isoenzyme changes in several models of rat cardiac hypertrophy. Circ. Res. 49: 525–532, 1981.
 342. Meredith, C. N., M. J. Zackin, W. R. Frontera, and W. J. Evans. Body composition and aerobic capacity in young and middle‐aged endurance‐trained men. Med. Sci. Sports Exerc. 19: 557–563, 1987.
 343. Merillon, J. P., G. Motte, C. Masquet, I. Azancot, A. Guiomard, and R. Gourgon. Relationship between physical properties of the arterial system and left ventricular performance in the course of aging and arterial hypertension. Eur. Heart J. 3 (suppl. A): 95–102, 1982.
 344. Messerli, F. H., E. D. Frohlich, D. H. Suarez, E. Reisin, G. R. Dreslinsky, F. G. Dunn, and F. E. Cole. Borderline hypertension: relationship between age, hemodynamics and circulating catecholamines. Circulation 64: 760–764, 1981.
 345. Messerli, F. H., Sundgaard‐Riise, H. O. Ventura, F. G. Dunn, W. Oigman, and E. D. Frohlich. Clinical and hemodynamic determinants of left ventricular dimensions. Arch. Intern. Med. 144: 477–481 1984.
 346. Miller, T. R., S. J. Grossman, K. B. Schectman, D. R. Biello, P. A. Ludbrook, and A. A. Ehsani. Left ventricular diastolic filling and its association with age. Am. J. Cardiol. 58: 531–535, 1986.
 347. Milliken, M. C., J. Stray‐Gundersen, R. M. Peshock, J. Katz, and J. H. Mitchell. Left ventricular mass as determined by magnetic resonance imaging in male endurance athletes. Am. J. Cardiol. 62: 301–305, 1988.
 348. Milnor, W. R. Hemodynamics. Baltimore: Williams and Wilkins, 1982.
 349. Mirsky, I., and M. M. Laks. Time course of changes in the mechanical properties of the canine right and left ventricles during hypertrophy caused by pressure overload. Circ. Res. 46: 530–542, 1980.
 350. Mitchell, J. H., B. J. Sproule and C. B. Chapman. The physiological meaning of the maximal oxygen intake test. J. Clin. Intest. 37: 538–547, 1958.
 351. Mithoefer, J. C., and M. S. Karetzky. Surgery of the Aged and Debilitated Patient. Philadelphia: J. H. Powers, 1968, p. 765–779.
 352. Miyatake, K., M. Okamoto, N. Kinoshita, M. Owa, I. Nakasone, H. Sakakibara, and Y. Nimura. Augmentation of atrial contribution to left ventricular inflow with aging as assessed by intracardiac Doppler flowmetry. Am. J. Cardiol. 53: 586–589, 1984.
 353. Mochly‐Rosen, D., C. J. Henrich, L. Cheever, H. Khaner, and P. C. Simpson. A protein kinase C isozyme is translocated to cytoskeletal elements on activation. Cell Reg. 1: 693–706, 1990.
 354. Morgan, H. E., and K. M. Baker. Cardiac hypertrophy. Mechanical, neural, and endocrine dependence. Circulation 83: 13–25, 1991.
 355. Mulvagh, S. L., L. H. Michael, M. B. Perryman, R. Roberts, and M. D. Schneider. A hemodynamic load in vivo induces cardiac expression of the cellular oncogene, c‐myc. Biochem. Biophys. Res. Commun. 147: 627–636, 1987.
 356. Murgo, J. P., N. Westerhof, J. P. Giolma, and S. A. Altobelli. Aortic input impedance in normal man: relationship to pressure wave forms. Circulation 62: 105–116, 1980.
 357. Murgo, J. P., N. Westerhof, J. P. Giolma, and S. A. Altobelli. Effects of exercise on aortic input impedance and pressure wave forms in normal humans. Circ. Res. 48: 334–343, 1981.
 358. Nagai, R., A. Zarain‐Herzberg, C. J. Brandl, J. Fujii, M. Tada, D. H. Maclennan, N. R. Alpert, and M. Periasamy. Regulation of myocardial Ca2+‐ATPase and phospholamban mRNA expression in response to pressure overload and thyroid hormone. Proc. Natl. Acad. Sci. U.S.A. 86: 2966–2970, 1989.
 359. Nakashima, T., and J. Tanikawa. A study of human aortic distensibility with relations to atherosclerosis and aging. Angiology 22: 477–490, 1971.
 360. Narayanan, N. Differential alterations in ATP‐supported calcium transport activities of sarcoplasmic reticulum and sarcolemma of aging myocardium. Biochim. Biophys. Acta. 678: 442–459, 1981.
 361. Narayanan, N., and J. A. Derby. Alterations in the properties of beta‐adrenergic receptors of myocardial membranes in aging: impairment of agonist‐receptor interactions and guanine nucleotide regulation accompany diminished catecholamine‐respon‐siveness of adenylate cyclase. Mech. Ageing Dev. 19: 127–139, 1982.
 362. Nichols, W. W., and C. J. Pepine. Left ventricular afterload and aortic input impedance: implications of pulsatile blood flow. Prog. Cardiovasc. Dis. 24: 293–306, 1982.
 363. Nichols, W. W., M. F. O'Rourke, A. P. Avolio, T. Yaginuma, J. P. Murgo, C. J. Pepine, and C. R. Conti. Effects of age on ventricular‐vascular coupling. Am. J. Cardiol. 55: 1179–1184, 1985.
 364. Nichols, W. W., M. F. O'Rourke, A. P. Avolio, T. Yaginuma, C. J. Pepine, and C. R. Conti. Ventricular/vascular interaction in patients with mild systemic hypertension and normal peripheral resistance. Circulation 74: 455–462, 1986.
 365. Nichols, W. W., M. F. O'Rourke, A. P. Avolio, T. Yaginuma, J. P. Murgo, C. J. Pepine, and C. R. Conti. Age‐related changes in left ventricular/arterial coupling. In: Ventricular Vascular Coupling: Clinical Physiology, and Engineering Aspects, edited by F. C. P. Yin. New York: Springer‐Verlag, 1987, p. 79–114.
 366. Nichols, W. W., C. J. Pepine, R. L. Feldman, J. Whittle, J. H. Selby, T. Kelly, and C. R. Conti. Influence of changes in pulsatile components of vascular load on left ventricular function: power‐load relations in patients without heart failure [Abstract]. Circulation 59/60: II–94, 1979.
 367. Nixon, J. V., H. Hallmark, K. Page, P. R. Raven, and J. H. Mitchell. Ventricular performance in human hearts aged 61 to 73 years. Am. J. Cardiol. 56: 932–937, 1985.
 368. O'Connor, S. W., P. J. Scarpace, and I. B. Abrass. Age‐associated decrease of adenylate cyclase activity in rat myocardium. Mech. Ageing Dev. 16: 91–95, 1981.
 369. O'Connor, S. W., P. J. Scarpace, and I. B. Abrass. Age‐associated decrease in the catalytic unit activity of rat myocardial adenylate cyclase. Mech. Ageing Dev. 21: 357–363, 1983.
 370. O'Donnell, S. R., and J. C. Wanstall. Demonstration of both β1 ‐ and β2‐adrenoceptor mediating relaxation of isolated ring preparations of rat pulmonary artery. Br. J. Pharmacol. 74: 547–552, 1981.
 371. O'Donnell, S. R., and J. C. Wanstall. Beta‐1 and beta‐2 adrenoceptor‐mediated responses in preparations of pulmonary artery and aorta from young and aged rats. J. Pharmacol. Exp. Ther. 228: 733–738, 1984.
 372. O'Donnell, S. R., and J. C. Wanstall. Thyroxine treatment of aged or young rats demonstrates that vascular responses mediated by β‐adrenoceptor sybtypes can be differentially regulated. Br. J. Pharmacol. 88: 41–49, 1986.
 373. O'Donnell, S. R., and J. C. Wanstall. Functional evidence for differential regulation of β‐adrenoceptor subtypes. Trends Pharmacol. Sci. 8: 265–268, 1987.
 374. Ogawa, T., R. J. Spina, W. H. Martin, III, W. M. Hohrt, K. B. Schechtman, J. O. Holloszy, and A. A. Ehsani. Effects of aging, sex, and physical training on cardiovascular responses to exercise. Circulation 86: 494–503, 1992.
 375. Olivetti, G., M. Melissari, J. M. Capasso, and P. Anversa. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ. Res. 68: 1560–1568, 1991.
 376. O'Neill, L., N. J. Holbrook, J. Fargnoli, and E. G. Lakatta. Progressive changes from young adult age to senescence in mRNA for rat cardiac myosin heavy chain genes. Cardioscience 2: 1–5, 1991.
 377. Orchard, C. H., and E. G. Lakatta. Intracellular calcium transients and developed tensions in rat heart muscle. A mechanism for the negative interval‐strength relationship. J. Gen. Physiol. 86: 637–651, 1985.
 378. Orlander, J., K. H. Kiessling, L. Larsson, J. Karlsson, and A. Aniansson. Skeletal muscle metabolism and ultrastructure in relation to age in sedentary men. Acta. Physiol. Scand. 104: 249–261, 1978.
 379. Orlowski, J., and J. B. Lingrel. Differential expression of the Na, K‐ATPase α1 and α2 subunit genes in murine myogenic cell line. Induction of the α2 isozyme during myocyte differentiation. J. Biol. Chem. 263: 17817–17821, 1988.
 380. O'Rourke, M. F. Arterial Function in Health and Disease. New York: Churchill Livingstone, 1982, p. 275.
 381. O'Rourke, M. F. Vascular impedance in studies of arterial and cardiac function. Physiol. Rev. 62: 570–623, 1982.
 382. Oscai, L. B., P. A. Mole, and J. O. Holloszy. Effects of exercise on cardiac weight and mitochondria in male and female rats. Am. J. Physiol. 220: 1944–1948, 1971.
 383. Pan, H. Y., B. B. Hoffman, R. A. Pershe, and T. F. Blaschke. Decline in beta adrenergic receptor‐mediated vascular relaxation with aging in man. J. Pharmacol. Exp. Ther. 239: 802–807, 1986.
 384. Peng, M. T., and M. Kang. Circadian rhythms and patterns of running‐wheel activity, feeding and drinking behaviors of old rats. Physiol. Behav. 33: 615–620, 1984.
 385. Penpargkul, S., F. Fein, E. H. Sonnenblick, and J. Scheuer. Depressed cardiac sarcoplasmic reticular function from diabetic rats. J. Mol. Cell. Cardiol. 13: 303–309, 1981.
 386. Peterson, L. H., R. E. Jensen, and J. Parnell. Mechanical properties of arteries in vivo. Circ. Res. 8: 622–639, 1960.
 387. Petrofsky, J. S., and A. R. Lind. Isometric strength, endurance, and the blood pressure and heart rate responses during isometric exercise in healthy men and women, with special reference to age and body fat content. Pflugers Arch. 360: 49–61, 1975.
 388. Pfeiffer, J. M., M. A. Pfeiffer, M. C. Fishbein, and E. D. Frohlich. Cardiac function and morphology with aging in the spontaneously hypertensive rat. Am. J. Physiol. 237 (Heart Circ. Physiol. 8): H461–H468, 1979.
 389. Pfeifer, M. A., C. R. Weinberg, D. Cook, J. D. Best, A. Reenan, and J. B. Halter. Differential changes of autonomic nervous system function with age in man. Am. J. Med. 75: 249–258, 1983.
 390. Pickering, G. W. High Blood Pressure. London: Churchill, 1955, p. 154–183.
 391. Pollock, M. L., C. Foster, D. O. Knapp, J. L. Rod, and D. H. Schmidt. Effect of age and training on aerobic capacity and body composition of master athletes. J. Appl. Physiol. 62: 725–731, 1987.
 392. Pollock, M. L., H. S. Miller, Jr., and J. Wilmore. Physiological characteristics of champion American track athletes 40 to 75 years of age. J. Gerontol. 29: 645–649, 1974.
 393. Pooling Project Research Group. Relationship of blood pressure, serum cholesterol, smoking, relative weight and ECG abnormalities to incidence of major coronary events: final report of the pooling project. J. Chron. Dis. 31: 201–306, 1978.
 394. Port, S., F. R. Cobb, R. E. Coleman, and R. H. Jones. Effect of age on the response of the left ventricular ejection fraction to exercise. N. Engl. J. Med. 303: 1113–1117, 1980.
 395. Porth, C. J., L. Groban, and J. J. Smith. Carotid‐cardiac baroreflex rseponses decrease with early aging in women [Abstract]. Physiologist 28: 350, 1985.
 396. Potter, J. F., D. Elahi, J. D. Tobin, and R. Andres. Effect of aging on the cardiothoracic ratio of men. J. Am. Geriatr. Soc. 30: 404–409, 1982.
 397. Prinz, P. N., J. Halter, C. Benedetti, and M. Raskind. Circadian variation of plasma catecholamines in young and old men: relation to rapid eye movement and slow wave sleep. J. Clin. Endocrinol. Metab. 49: 300–304, 1979.
 398. Proper, R., and F. Wall. Left ventricular stroke volume measurements not affected by chronologic aging. Am. Heart J. 83: 843–845, 1972.
 399. Rakusan, K., and O. Poupa. Capillaries and muscle fibers in the heart of old rats. Gerontologia 9: 107–112, 1964.
 400. Randall, O., M. Esler, B. Culp, S. Julius, and A. Zwifler. Determinants of baroreflex sensitivity in man. Lab. Clin. Med. 91: 514–519, 1978.
 401. Raven, P. B., and J. Mitchell. The effect of aging on the cardiovascular response to dynamic and static exercise. In: The Aging Heart, edited by M. L. Weisfeldt. New York: Raven Press, 1980, p. 269–296.
 402. Reaven, E. P., and G. M. Reaven. Structure and function changes in the endocrine pancreas of aging rats with reference to the modulating effects of exercise and caloric restriction. J. Clin. Invest. 68: 75–84, 1981.
 403. Reithmann, C., P. Gierschik, U. Müller, K. Werdan, and K. H. Jakobs. Pseudomonas exotoxin A prevents β‐adrenocep‐tor‐induced upregulation of Gi protein α‐subunits and adenylyl cyclase desensitization in rat heart muscle cells. Mol. Pharmacol. 37: 631–638, 1990.
 404. Reithmann, C., P. Gierschik, D. Sidiropoulos, K. Werdan, and K. H. Jakobs. Mechanism of noradrenaline‐induced heterologous desensitization of adenylate cyclase stimulation in rat heart muscle cells: increase in the level of inhibitory G‐protein α‐subunits. Eur. J. Pharmacol. 172: 211–221, 1989.
 405. Remington, J. W., The physiology of the aorta and major arteries. In: Handbook of Physiology. Circulation II, edited by W. F. Hamilton and P. Dow. Washington, DC: American Physiological Society, 1963, p. 808.
 406. Reneman, R. S., T. Van Merode, P. Hick, and A. P. G. Hoeks. Flow velocity patterns in and distensibility of the carotid artery bulb in subjects of various ages. Circulation 71: 500–509, 1985.
 407. Reneman, R. S., T. Van Merode, and A. P. G. Hoeks. Noninvasive assessment of arterial flow patterns and wall properties in humans. News Physiol. Sci. 4: 185–190, 1989.
 408. Renlund, D. G., G. Gerstenblith, J. L. Fleg, L. C. Becker, and E. G. Lakatta. Interaction between left ventricular end‐diastolic and end‐systolic volumes in normal humans. Am. J. Physiol. 258 (Heart Circ. Physiol. 29): H473–H481, 1990.
 409. Renlund, D. G., G. Gerstenblith, R. J. Rodeheffer, J. L. Fleg, and E. K. Lakatta. Potency of the Frank Starling reverse in normal man [Abstract]. J. Am. Coll. Cardiol. 5: 514, 1985.
 410. Rerych, S. K., P. M. Scholz, D. C. Sabiston, Jr., and R. H. Jones. Effects of exercise training on left ventricular function in normal subjects: a longitudinal study by radionuclide angiography. Am. J. Cardiol. 45: 244–252, 1990.
 411. Rich, K. A., J. Codina, G. Floyd, R. Sekura, J. D. Hilde‐Brandt, and R. Iyengar. Glucagon‐induced heterologous desensitization of MDCK cell adenylyl cyclase. Increase in the apparent levels of the inhibitory regulator (Ni). J. Biol. Chem. 259: 7893–7901, 1984.
 412. Richardson, D. Effects of age on cutaneous circulatory response to direct heat on the forearm. J. Gerontol.: Med. Sci. 44: M189–M194, 1989.
 413. Riegger, G. A., D. Elsner, E. P. Kromer, C. Daffner, W. G. Forssmann, F. Muders, E. W. Pascher, and K. Kochsiek. Atrial natriuretic peptide in congestive heart failure in the dog: plasma levels, cyclic guanosine monophosphate, ultrastructure of atrial myoendocrine cells, and hemodynamic, hormonal, and renal effects. Circulation 77: 398–406, 1988.
 414. Roach, M. R., and A. C. Burton. The effect of age on the elasticity of human iliac arteries. Can. J. Biochem. Physiol. 37: 557–570, 1959.
 415. Robert, L., B. Robert, and A. M. Robert. Molecular biology of elastin as related to aging and atherosclerosis. Exp. Gerontol. 5: 339–356, 1970.
 416. Robinson, S. Experimental studies of physical fitness in relation to age. Arbeitsphysiologie 10: 251: 323, 1938.
 417. Robinson, S., D. B. Dill, R. D. Robinson, S. P. Tzankoff, and J. A. Wagner. Physiological aging of champion runners. J. Appl. Physiol. 41: 46–51, 1976.
 418. Rockoff, J. B., and J. G. Dobson, Jr.. Inhibition by adenosine of catecholamine‐induced increase in rat atrial contractility. Am. J. Physiol. 239 (Heart Circ. Physiol. 10): H365–H370, 1980.
 419. Rodbell, M. The role of hormone receptors and GTP‐regula‐tory proteins in membrane transduction. Nature 284: 17–22, 1980.
 420. Rodeheffer, R. J., G. Gerstenblith, E. Beard, J. L. Fleg, L. C. Becker, M. L. Weisfeldt, and E. G. Lakatta. Postural changes in cardiac volumes in men in relation to adult age. Exp. Gerontol. 21: 367–378, 1986.
 421. Rodeheffer, R. J., G. Gerstenblith, L. C. Becker, J. L. Fleg, M. L. Weisfeldt, and E. G. Lakatta. Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for a diminished heart rate. Circulation 69: 203–213, 1984.
 422. Rogers, M. A., J. M. Hagberg, W. H. Martin, III, A. A. Ehsani, and J. O. Holloszy. Decline in VO2max with aging in master athletes and sedentary men. J. Appl. Physiol. 68: 2195–2199, 1990.
 423. Rothbaum, D. A., D. J. Shaw, C. S. Angell, and N. W. Shock. Cardiac performance in the unanesthetized senescent male rat. J. Gerontol. 28: 287–292, 1973.
 424. Rowe, J. W., and B. R. Troen. Sympathetic nervous system and aging in man. Endocr. Rev. 1: 167–179, 1980.
 425. Rubin, P. C., P. J. Scott, K. McLean, and J. L. Reid. Noradrenaline release and clearance in relation to age and blood pressure in man. Eur. J. Clin. Invest. 12: 121–125, 1982.
 426. Ruch, S., W.‐B. Im, R. H. Kennedy, E. Seifen, and T. Akera. Aging: stimulation rate of cardiac intracellular Na+ activity and developed tension. Mech. Ageing Dev. 60: 303–313, 1991.
 427. Rupp, H. The adaptive changes in the isoenzyme pattern of myosin from hypertrophied rat myocardium as a result of pressure overload and physical training. Basic Res. Cardiol. 76: 79–88, 1981.
 428. Safar, M. E., J. J. Toto‐Moukouo, J. A. Bouthier, R. E. Asmar, J. A. Levenson, A. C. Simon, and G. M. London. Arterial dynamics, cardiac hypertrophy, and antihypertensive treatment. Circulation 75: I156–I161, 1987.
 429. Sagawa, K. The ventricular pressure‐volume diagram revisited. Circ. Res. 43: 678–687, 1978.
 430. Sagawa, K. Editorial: The pressure‐volume relation of the ventricle: definition, modifications and clinical use. Circulation 63: 1223–1227, 1981.
 431. Sakai, M., R. S. Danziger, J. M. Staddon, E. G. Lakatta, and R. G. Hansford. Decrease with senescence in the norepinephrine‐induced phosphorylation of myofilament proteins in isolated rat cardiac myocytes. J. Mol. Cell. Cardiol. 21: 1327–1336, 1989.
 432. Sakai, M., R. S. Danziger, R.‐P. Xiao, H. A. Spurgeon, and E. G. Lakatta. Contractile response of individual cardiac myocytes to norepinephrine declines with senescence. Am. J. Physiol. 262 (Heart Circ. Physiol. 33): H184–H189, 1992.
 433. Scamps, F., E. Mayoux, D. Charlemagne, and G. Vassort. Calcium current in single cells isolated from normal and hypertrophied rat heart. Effect of beta‐adrenergic stimulation. Circ. Res. 67: 199–208, 1990.
 434. Scarpace, P. J. Decreased β‐adrenergic responsiveness during senescence. Fed. Proc. 45: 51–54, 1986.
 435. Scarpace, P. J. Decreased receptor activation with age. Can it be explained by desensitization? J. Am. Geriatr. Soc. 36: 1067–1071, 1988.
 436. Scarpace, P. J. Forskolin activation of adenylate cyclase in rat myocardium with age: effects of guanine nucleotide analogs. Mech. Ageing Dev. 52: 169–178, 1990.
 437. Scarpace, P. J., and I. B. Abrass. Decreased beta‐adrenergic agonist affinity and adenylate cyclase activity in senescent rat lung. J. Gerontol. 38: 143–147, 1983.
 438. Scarpace, P. J., and I. B. Abrass. Beta‐adrenergic agonist‐mediated desensitization in senescent rats. Mech. Ageing Dev. 35: 255–264, 1986.
 439. Scarpace, P. J., and L. A. Baresi. Increased beta‐adrenergic receptors in the light‐density membrane fraction in lungs from senescent rats. J. Gerontol. 43: B163–B167, 1988.
 440. Schaffer, S. W., S. Allo, S. Pumma, and T. White. Defective response to cAMP‐dependent protein kinase in non‐insulin‐dependent diabetic heart. Am. J. Physiol. 261 (Endocrinol. Metab. 24): E369–E376, 1991.
 441. Schaffer, S. W., M. S. Mozaffari, M. Artman, and G. L. Wilson. Basis for myocardial mechanical defects associated with non‐insulin‐dependent diabetes. Am. J. Physiol. 256 (Endocrinol. Metab. 19): E25–E30, 1989.
 442. Scheuer, J., A. Malhotra, C. Hirsch, J. Capasso, and T. F. Schaible. Physiologic cardiac hypertrophy corrects contractile protein abnormalities associated with pathologic hypertrophy in rats. J. Clin. Invest. 70: 1300–1305, 1982.
 443. Schiaffino, S., J. L. Samuel, D. Sassoon, A. M. Lompre, I. Garner, F. Marott, M. Buckingham, L. Rappaport, and K. Schwartz. Non‐synchronous accumulation of α1 skeletal actin and β‐myosin heavy chain mRNAs during early stages of pressure‐overload‐induced cardiac hypertrophy demonstrated by in situ hybridization. Circ. Res. 64: 937–948, 1989.
 444. Schneider, M. D., and T. G. Parker. Cardiac myocytes as targets for the action of peptide growth factors. Circulation 81: 1443–1456, 1990.
 445. Schocken, D. D., J. A. Blumenthal, S. Port, P. Hindle, and R. E. Coleman. Physical conditioning and left ventricular performance in the elderly: assessment by radionuclide angiocardiography. Am. J. Cardiol. 52: 359–364, 1983.
 446. Schoeffter, P., and J.‐C. Stoclet. Age‐related differences in cyclic AMP metabolism and their consequences on relaxation induced by isoproterenol and phosphodiesterase inhibitors in rat isolated aorta. Mech. Ageing Dev. 54: 197–205, 1990.
 447. Schrader, J., G. Baumann, and E. Gerlach. Adenosine as inhibitor of myocardial effects of catecholamines. Pflugers Arch. 372: 29–35, 1977.
 448. Schulman, S., E. G. Lakatta, J. L. Fleg, L. Lakatta, L. C. Becker, and G. Gerstenblith. Age‐related decline in left ventricular filling at rest and exercise. Am. J. Physiol. 263 (Heart Circ. Physiol. 34): H1932–H1938, 1992.
 449. Schulman, S. P., J. L. Weiss, L. C. Becker, S. O. Gottlieb, K. M. Woodruff, M. L. Weisfeldt, and G. Gerstenblith. The effects of antihypertensive therapy on left ventricular mass in elderly patients. N. Engl. J. Med. 322: 1350–1356, 1990.
 450. Schuyler, G. T., and L. R. Yarbrough. Comparison of myosin and creatine kinase isoforms in left ventricles of young and senescent Fischer 344 rats after treatment with triiodothyronine. Mech. Ageing Dev. 56: 39–48, 1990.
 451. Schwartz, J. B., W. J. Gibb, and T. Tran. Aging effects on heart rate variation. J. Gerontol.: Med. Sci. 46: M99–M106, 1991.
 452. Schwartz, K., A. M. Lompre, D. de la Bastie, and J. J. Mercadier. Mechanogenic transduction in the hypertrophied heart [Abstract]. J. Mol. Cell. Cardiol. 21 (suppl. III): S.24, 1989.
 453. Scott, P. J., and J. L. Reid. The effect of age on the responses of human isolated arteries to noradrenaline. Br. J. Clin. Pharmacol. 13: 237–239, 1982.
 454. Seals, D. R., and P. B. Chase. Influence of physical training on heart rate variability and baroreflex circulatory control. J. Appl. Physiol. 66: 1886–1895, 1989.
 455. Seals, D. R., J. M. Haberg, B. F. Hurley, A. A. Ehsani, and J. O. Holloszy. Endurance training in older men and women. I. Cardiovascular responses to exercise. J. Appl. Physiol. 57: 1024–1029, 1984.
 456. Seidman, C. E. Expression of atrial natriuretic factor in the normal and hypertrophied heart. Heart Failure 5: 130–134, 1989.
 457. Seligman, M., R. F. Eilberg, and L. Fishman. Mineralization of elastin extracted from human aortic tissues. Calcif. Tiss. Res. 17: 229–234, 1975.
 458. Shannon, R. P., K. A. Maher, J. T. Santinga, H. D. Royal, and J. Y. Wei. Comparison of differences in the hemodynamic response to passive postural stress in healthy subjects > 70 years and < 30 years of age. Am. J. Cardiol. 67: 1110–1116, 1991.
 459. Shannon, R. P., J. Y. Wei, R. M. Rosa, F. H. Epstein, and J. W. Rowe. The effect of age and sodium depletion on cardiovascular response to orthostasis. Hypertension 8: 438–443, 1986.
 460. Shechter, J. A., T. D. Friehling, C. Uboh, G. J. Kelliher, K. M. O'Connor, and P. R. Kowey. The effect of left ventricular hypertrophy on inducible ventricular arrhythmias [Abstract]. Circulation 70: II–234, 1984.
 461. Shimada, K., T. Kitazumi, N. Sadakane, H. Ogura, and T. Ozawa. Age‐related changes of baroreflex function, plasma norepinephrine, and blood pressure. Hypertension 7: 113–117, 1985.
 462. Shiverick, C. T., B. B. Hamrell, and N. R. Alpert. Structural and functional properties of myosin associated with the compensatory cardiac hypertrophy in the rabbit. J. Mol. Cell. Cardiol. 8: 837–851, 1976.
 463. Shreiner, D. P., M. L. Weisfeldt, and N. W. Shock. Effects of age, sex, and breeding status on the rat heart. Am. J. Physiol. 217: 176–180, 1969.
 464. Sibley, D. R., and R. J. Lefkowitz. Molecular mechanisms of receptor desensitization using the β‐adrenergic receptor‐coupled adenylate cyclase system as a model. Nature 317: 124–129, 1985.
 465. Simon, A. C., J. A. Levenson, J. L. Bouthier, and M. E. Safar. Captopril‐induced changes in large arteries in essential hypertension. Am. J. Med. 76: 71–75, 1984.
 466. Simpson, D. M., and R. Wicks. Spectral analysis of heart rate indicated reduced baroreceptor‐related heart rate variability in elderly persons. J. Gerontol.: Med. Sci. 43: M21–M24, 1988.
 467. Simpson, P. Stimulation of hypertrophy of cultured neonatal rat heart cells through an α1‐adrenergic receptor interaction. Evidence for independent regulation of growth beating. Circ. Res. 56: 884–894, 1985.
 468. Simpson, P. C. Molecular mechanisms in myocardial hypertrophy. Heart Failure 5: 113–129, 1989a.
 469. Simpson, P. C. Proto‐oncogenes and cardiac hypertrophy. Ann. Rev. Physiol. 51: 189–202, 1989b.
 470. Siri, F. M., J. Kureger, C. Nordin, Z. Ming, and R. S. Aronson. Depressed intracellular calcium transients and contraction in myocytes from hypertrophied and failing guinea pig hearts. Am. J. Physiol. 261 (Heart Circ. Physiol. 32): H514–H530, 1991.
 471. Sjögren, A. L. Left ventricular wall thickness determined by ultrasound in 100 subjects without heart disease. Chest 60: 341–346, 1971.
 472. Smith, J. J., and C. J. M. Porth. Age and response to orthostatic stress. In: Circulatory Response to the Upright Posture, edited by J. J. Smith. Boca Raton: FL: CRC Press, 1990, p. 1–46.
 473. Smith, J. J., J. A. Barney, L. Groban, A. Stadnicks, and T. J. Ebert. Carotid‐cardiac baroreflex responses decrease with early aging in man [Abstract]. Fed. Proc. 44: 1887, 1985.
 474. Smith, M. L., and P. B. Raven. Cardiovascular responses to lower body negative pressure in endurance and static exercise‐trained men. Med. Sci. Sports Exerc. 18: 545–550, 1986.
 475. Smith, M. L., H. M. Graitzer, D. L. Hudson, and P. B. Raven. Baroreflex function in endurance‐ and static exercise‐trained men. J. Appl. Physiol. 64: 585–591, 1988.
 476. Smith, S. A., and J. J. Fasler. Age‐related changes in autonomic function: relationship with postural hypotension. Age Ageing 12: 206–210, 1983.
 477. Smith, V. E., G. H. Rutan, and L. H. Kuller. LV mass is best predicted by systolic ambulatory blood pressure in the elderly [Abstract]. J. Am. Coll. Cardiol. 17: 269A.
 478. Smith, V. E., P. Schulman, M. K. Karimeddini, W. B. White, M. K. Meeran, and A. M. Katz. Rapid ventricular filling in left ventricular hypertrophy II. Pathologic hypertrophy. J. Am. Coll. Cardiol. 5: 869–874, 1985.
 479. Smith, V. E., W. B. White, and M. K. Karmeddini. Echocardiography assessment of left ventricular diastolic performance in hypertensive subjects: correlation with changes in left ventricular mass. Hypertension 9 (suppl. 2): II81–II84, 1987.
 480. Smulyan, H., T. J. Csermely, S. Mookherjee, and R. A. Warner. Effect of age on arterial distensibility in asymptomatic humans. Arteriosclerosis 3: 199–205, 1983.
 481. Sowers, J. R., and P. K. Mohanty. Effect of advancing age on cardiopulmonary baroreceptor function in hypertensive men. Hypertension 10: 274–279, 1987.
 482. Sowers, J. R., L Z. Rubenstein, and N. Stern. Plasma norepinephrine responses to posture and isometric exercise increase with age in the absence of obesity. J. Gerontol. 38: 315–317, 1983.
 483. Spina, R. J., R. Ogawa, W. M. Kohrt, W. H. Martin, III, J. O. Holloszy, and A. A. Ehsani. Differences in cardiovascular adaptations to endurance exercise training between older men and women. J. Appl. Physiol. 75: 849–855.
 484. Spirito, P., and B. J. Maron. Influence of aging on Doppler echocardiographic indices on left ventricular diastolic function. Br. Heart J. 59: 672–679, 1988.
 485. Spurgeon, H. A., duBell, M. Boyett, A. Talo, M. C. Capogrossi, and E. G. Lakatta. Cytosolic Ca2+ modulation of membrane potential during a heart beat: perspectives from the single cardiac cell [Abstract]. J. Mol. Cell. Cardiol. 21: S. 19, 1989.
 486. Spurgeon, H. A., M. F. Steinbach, and E. G. Lakatta. Chronic exercise prevents characteristic age‐related changed in rat cardiac contraction. Am. J. Physiol. 244 (Heart Circ. Physiol. 15): H513–H518, 1983.
 487. Spurgeon, H. A., P. R. Thorne, F. C. P. Yin, N. W. Shock, and M. F. Weisfeldt. Increased dynamic stiffness of trabeculae carneae from senescent rats. Am. J. Physiol. 232 (Heart Circ. Physiol. 3): H373–380, 1977.
 488. Starke, K. Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol. Biochem. Pharmacol. 77: 1–124, 1977.
 489. Starnes, J. W., and W. L. Rumsey. Cardiac energetics and performance of exercised and food‐restricted rats during aging. Am. J. Physiol. 254 (Heart Circ. Physiol. 25): H599–H608, 1988.
 490. Starnes, J. W., R. E. Beyer, and D. W. Edington. Myocardial adaptations to endurance exercise in aged rats. Am. J. Physiol. 245 (Heart Circ. Physiol. 16): H560–H566, 1983.
 491. Steinnhagen‐Theissen, E., A. Z. Reznick, and J. D. Ringe. Age dependent variations in cardiac and skeletal muscle during short and long term transmill‐running of mice. Eur. Heart J. 5 (suppl. E): 37–30, 1984.
 492. Stern, M. D., A. A. Kort, G. M. Bhatnager, and E. G. Lakatta. Scattered‐light intensity fluctuations in diastolic rat cardiac muscle caused by spontaneous Ca++‐dependent cellular mechanical oscillations. J. Gen. Physiol. 82: 119–153, 1983.
 493. Stessman, J., R. Eliakim, C. Cahan, and R. P. Ebstein. Deterioration of beta‐receptor‐adenylate cyclase function in elderly, hospitalized patients. J. Gerontol. 39: 667–672, 1984.
 494. Strandell, T. Heart volume and its relation to anthropometric data in old men compared with young men. Acta Med. Scand. 176: 205–218, 1964a.
 495. Strandell, T. Total haemoglobin, blood volume and haemoglobin concentration at rest and circulatory adaptation during exercise in relation to some anthropometric data in old men compared with young men. Acta Med. Scand. 176: 219–232, 1964b.
 496. Strandell, T. Circulatory studies on healthy old men. With special reference to the limitation of the maximal physical working capacity. Acta Med. Scand. 175 (414): 1–44, 1964c.
 497. Strasser, R. H., R. A. Cerione, J. Codina, M. G. Caron, and R. J. Lefkowitz. Homologous desensitization of the beta‐adrenergic receptor. Functional integrity of the desensitized receptor from mammalian lung. Mol. Pharmacol. 28: 237–245, 1985.
 498. Strasser, R. H., D. R. Sibley, and R. J. Lefkowitz. A novel catecholamine‐activated adenosine cyclic 3′,5′‐phosphate independent pathway for β‐adrenergic receptor phosphorylation in wild‐type and mutant S49 lymphoma cells: mechanism of homologous desensitization of adenylate cyclase. Biochemistry 25: 1371–1377, 1986.
 499. Strasser, R. H., G. L. Stiles, and R. J Lefkowitz. Translocation and uncoupling of the beta‐adrenergic receptor in rat lung after catecholamine promoted desensitization in vivo. Endocrinology 115: 1392–1400, 1984.
 500. Stratton, J. R., M. D. Cerquerira, R. S. Schwartz, W. C. Levy, R. C. Veith, S. E. Kahn, and I. B. Abrass. Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men. Circulation 86: 504–512, 1992.
 501. Strehler, B. L., D. D. Mark, A. S. Mildvan, and M. V. Gee. Rate and magnitude of age pigment accumulation in the human myocardium. J. Gerontol. 14: 430–439, 1959.
 502. Sullivan, M. J., F. R. Cobb, and M. B. Higginbotham. Stroke volume increases by similar mechanisms during upright exercise in normal men and women. Am. J. Cardiol. 67: 1405–1412, 1991.
 503. Sunagawa, K., W. L. Maughan, and K. Sagawa. Optimal arterial resistance for the maximal stroke work studied in isolated canine left ventricle. Circ. Res. 56: 586–595, 1985.
 504. Supiano, M. A., O. A. Linares, J. B. Halter, K. M. Reno, and S. G. Rosen. Functional uncoupling of the platelet α2‐adrenergic receptor‐adenylate cyclase complex in the elderly. J. Clin. Endocrinol. Metab. 64: 1160–1164, 1987.
 505. Supiano, M. A., R. R. Neubig, O. A. Linares, J. B. Halter, and S. G. Rosen. Effects of low‐sodium diet on regulation of platelet α2‐adrenergic receptors in young and elderly humans. Am. J. Physiol. 256 (Endocrinol. Metab. 19): E399–E344, 1989.
 506. Sutton, M. S., S. N. Reichek, J. Lovett, J. A. Kastor, and E. Guiliani. Effects of age, body size and blood pressure on the normal human left ventricle [Abstract]. Circulation 62: III–305, 1980.
 507. Swinne, C. J., E. P. Shapiro, S. D. Lima, and J. L. Fleg. Age‐associated changes in left ventricular diastolic performance during isometric exercise in normal subjects. Am. J. Cardiol. 69: 823–826, 1992.
 508. Swynghedauw, B. Remodelling of the heart in response to chronic mechanical overload. Eur. Heart J. 10: 935–943, 1989.
 509. Taffet, G. E., and C. A. Tate. The sarcoplasmic reticulum calcium ATPase from rat heart is decreased in senescence [Abstract]. Gerontologist 30: 111A, 1990.
 510. Takahashi, T., H. Schunkert, S. Isoyama, J. Y. Wei, B. Nadal‐Ginard, W. Grossman, and S. Izumo. Age‐related differences in the expression of proto‐oncogene and contractile protein genes in response to pressure overload in the rat myocardium. J. Clin. Invest. 89: 939–946, 1992.
 511. Tankersley, C. G., J. Smolander, W. L. Kennedy, and S. M. Fortney. Sweating and skin blood flow during exercise: effects of age and maximal oxygen uptake. J. Appl. Physiol. 71: 236–242, 1991.
 512. Tate, C. A., G. E. Taffet, E. K. Hudson, S. L. Blaylock, R. P. McBride, and L. H. Michael. Enhanced calcium uptake of cardiac sarcoplasmic reticulum in exercise‐trained old rats. Am. J. Physiol. 258 (Heart Circ. Physiol. 29): H431–H435, 1990.
 513. Tawney, K. W., E. C. Johnson, and E. R. Greene. Age‐related differences in reactivity of the central circulation to head‐up tilt [Abstract]. Physiologist 31: A130, 1988.
 514. Taylor, D. J., M. Crowe, P. J. Bore, P. Styles, D. L. Arnold, and G. K. Radda. Examination of the energetics of aging skeletal muscle using nuclear magnetic resonance. Gerontology 30: 2–7, 1984.
 515. Taylor, J. A., G. A. Hand, D. G. Johnson, and D. R. Seals. Augmented forearm vasoconstriction during dynamic exercise in healthy older men. Circulation 86: 1789–1799, 1992.
 516. Templeton, G. H., M. R. Platt, J. T. Willerson, and M.L. Weisfeldt. Influence of aging on left ventricular hemodynamics and stiffness in beagles. Circ. Res. 44: 189–194, 1979.
 517. Ting, C. T., K. P. Brin, S. J. Lin, S. P. Wang, M. S. Chang, B. N. Chiang, and F. C. Yin. Arterial hemodynamics in human hypertension. J. Clin. Invest. 78: 1462–1471, 1986.
 518. Toda, N., and M. Miyazaki. Senescent beagle coronary arteries in response to catecholamines and adrenergic nerve stimulation. J. Gerontol. 42: 210–218, 1987.
 519. Tomanek, R. J. Effects of age and exercise on the extent of the myocardial capillary bed. Anat. Rec. 167: 55–62, 1970.
 520. Tomanek, R. J., and J. M. Hovanec. The effects of long‐term pressure‐overload and aging on the myocardium. J. Mol. Cell. Cardiol. 13: 471–488, 1981.
 521. Tomanek, R. J., and U. L. Karlsson. Myocardial ultrastructure of young and senescent rats. J. Ultrastruc. Res. 42: 201–220, 1973.
 522. Topol, E. J., T. A. Traill, and N. J. Fortuin. Hypertensive hypertrophic cardiomyopathy of the elderly. N. Engl. J. Med. 312: 277–183, 1985.
 523. Travis, D. F., and A. Travis. Ultrasound changes in the left ventricular rat myocardial cells with age. J. Ultrastruct. Res. 39: 124–148, 1972.
 524. Tsujimoto, G., C.‐H. Lee, and B. B Hoffman. Age‐related decrease in beta adrenergic receptor‐mediated vascular smooth muscle relaxation. J. Pharmacol. Exp. Ther. 239: 411–415, 1986.
 525. Tzankoff, S. P., and A. H. Norris. Effect of muscle mass decrease on age‐related BMR changes. J. Appl. Physiol. 43: 1001–1006, 1977.
 526. Unverferth, D. V., J. K. Fetters, B. J. Unverferth, C. V. Leier, R. D. Magorien, A. R. Arn, and P. B. Baker. Human myocardial histologic characteristics in congestive heart failure. Circulation 68: 1194–1200, 1983.
 527. Vaitkevicius, P. V., J. L. Fleg, J. H. Engel, F. C. O'Connor, J. G. Wright, L. E. Lakatta, F. C.‐P. Yin, and E. G. Lakatta. Efects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation 88: 1456–1462, 1993.
 528. Van Brummelen, P., F. R. Buhler, W. Kiowski, and F. W. Amann. Age‐related decrease in cardiac and peripheral vascular responsiveness to isoprenaline: studies in normal subjects. Clin. Sci. 60: 571–577, 1981.
 529. Vantosh, A., E. G. Lakatta, J. L. Fleg, J. Weiss, C. Kallman, M. Weisfeldt, and G. Gerstenblith. Ventricular dimensional changes during submaximal exercise: effect of aging in normal man [Abstract]. Circulation 62: III–129, 1980.
 530. Veith, R. C., J. D. Best, and J. B. Halter. Dose‐dependent suppression of norepinephrine appearance rate in plasma by clonidine in man. J. Clin. Endocrinol. Metab. 59: 151–155, 1984.
 531. Ventura‐Clapier, R., H. Mekhfi, P. Oliviero, and B. Swynghedauw. Pressure overload changes cardiac skinned‐fiber mechanics in rats, not in guinea pigs. Am. J. Physiol. 254 (Heart Circ. Physiol. 25): H517–524, 1988.
 532. Verkhratsky, N. S. Acetylcholine metabolism peculiarities in aging. Exp. Gerontol. 5: 49–56, 1970.
 533. Vestal, R. E., A. J. H. Wood, and D. G. Shand. Reduced beta‐adrenoreceptor sensitivity in the elderly. Clin. Pharmacol. Ther. 26: 181–186, 1979.
 534. Vizek, M., and I. Albrecht. Development of cardiac output in male rats. Physiol. Bohemoslov. 22: 573–580, 1973.
 535. Von Harsdorf, R., R. E. Lang, M. Fullerton, and E. A. Woodcock. Myocardial stretch stimulates phosphatidylinositol turnover. Circ. Res. 65: 494–501, 1989.
 536. Voutilainen, S., M. Kupari, M. hlppelainen, K. Karppinen, M. Ventila, and J. Heikkila. Factors influencing Doppler indexes of left ventricular filling in healthy persons. Am. J. Cardiol. 68: 653–659, 1991.
 537. Wahren, J., B. Salttn, L. Jorfeldt, and B. Pernow. Influence of age on the local circulatory adaptation to leg exercise. Scand. J. Clin. Lab. Invest. 33: 79–86, 1974.
 538. Walford, G. D., H. A. Spurgeon, and E. G. Lakatta. Diminished cardiac hypertrophy and muscle performance in older compared to younger adult rats with chronic atrioventricular block. Circ. Res. 63: 502–511, 1988.
 539. Walker, K. E., and S. R. Houser. Intracellular calcium buffers affect age‐related calcium current decay [Abstract]. Circulation 82: III–746, 1990.
 540. Walker, K. E., E. G. Lakatta, and S. R. Houser. Age associated changes in membrane currents in rat ventricular myocytes. Cardiovasc. Res. 27: 1968–1977, 1993.
 541. Waller, B. F., and W. C. Roberts. Cardiovascular disease in the very elderly. Analysis of 40 necropsy patients ages 90 years or over. Am. J. Cardiol. 51: 403–421, 1983.
 542. Watkins, S. C., J. L. Samuel, F. Marotte, B. Bertier‐Savalle, and L. Rappaport. Microtubules and desmin filaments during onset of heart hypertrophy in rat: a double immunoelectron microscope study. Circ. Res. 60: 327–336, 1987.
 543. Watson, P. A., T. Haneda, and H. E. Morgan. Effect of higher aortic pressure on ribosome formation and cAMP content in rat heart. Am. J. Physiol. 256 (Cell Physiol. 25): C1257–C1261, 1989.
 544. Wei, J. Y., Y. X. Li, T. Lincoln, W. Grossman, and D. Mendelowitz. Chronic exercise training protects aged cardiac muscle against hypoxia. J. Clin. Invest. 83: 778–784, 1989.
 545. Wei, J. Y., H. A. Spurgeon, and E. G. Lakatta. Excitation‐contraction in rat myocardium: alterations with adult aging. Am. J. Physiol. (Heart Circ. Physiol. 17): H784–H791, 1984.
 546. Weinberger, M. H., and N. S. Fineberg. Sodium and volume sensitivity of blood pressure. Age and pressure change over time. Hypertension 18: 67–71, 1991.
 547. Weisfeldt, M. L., W. A. Loeven, and N. W. Shock. Resting and active mechanical properties of trabeculae carneae from aged male rats Am. J. Physiol. 220: 1921–1927, 1971.
 548. Weisfeldt, M. L., J. R. Wright, D. P. Shreiner, E. Lakatta, and N. W. Shock. Coronary flow and oxygen extraction in the perfused heart of senescent male rats. J. Appl. Physiol. 30: 44–49, 1971.
 549. Wilens, S. L., and E. E. Sproul. Spontaneous cardiovascular disease in the rat. Am. J. Pathol. 14: 177–216, 1938.
 550. Wilson, J. R., P. Douglas, W. F. Hickey, V. Lanocoe, N. Ferraro, A. Muhammad, and N. Reichek. Experimental congestive heart failure produced by rapid ventricular pacing in the dog: cardiac effects. Circulation 75: 857–867, 1987.
 551. Wisenbaugh, T., P. Allen, G. Cooper, IV, W. N. O'Connor, L. Mezaros, R. Streter, A. Bahinski, S. Houser, and J. F. Spann. Hypertrophy without contractile dysfunction after reversal of pressure overload in the cat. Am. J. Physiol. 247 (Heart Circ. Physiol. 18): H146–H154, 1984.
 552. Wolf, H., and F. Hofmann. Purification of myosin light chain kinase from bovine cardiac muscle. Proc. Natl. Acad. Sci. U.S.A. 77: 5852–5855, 1980.
 553. Wolinsky, H. Long‐term effects of hypertension on the rat aortic wall and their relation to concurrent aging changes. Morphological and chemical studies. Circ. Res. 30: 301–309, 1972.
 554. Woodcock, E. A., J. W. Funder, and C. I. Johnston. Decreased cardiac β‐adrenergic receptors in deoxycorticosterone‐salt and renal hypertensive rats. Circ. Res. 45: 560–565, 1979.
 555. Xiao, R.‐P., and E. G. Lakatta. Mechanisms of altered β‐adrenergic modulation of the cardiovascular system with aging. Rev. Clin. Gerontol. 1: 309–322, 1991.
 556. Xiao, R.‐P., M. C. Capogrossi, H. A. Spurgeon, and E. G. Lakatta. Stimulation of 8 opioid receptors in single heart cells blocks β‐adrenergic receptor mediated increase in calcium and contraction [Abstract]. J. Mol. Cell. Cardiol. 23 (suppl. III): S83, 1991.
 557. Xiao, P.‐P., H. A. Spurgeon, F. O'Connor, and E. G. Lakatta. Age‐associated changes in beta‐adrenergic modulation on rat cardiac excitation‐contraction coupling. J. Clin. Invest. 1994 (in press).
 558. Yakovlev, V. M. Some data on the functional state of the arterial system in aged persons. Kardiologiia 11: 99–103, 1971.
 559. Yamada, Y., E. Miyajima, O. Tochikubo, T. Matsukawa, and M. Ishii. Age‐related changes in muscle sympathetic nerve activity in essential hypertension. Hypertension 13: 870–877, 1989.
 560. Yazaki, Y., and I. Komuro. Molecular analysis of cardiac hypertrophy due to overload [Abstract]. J. Mol. Cell. Cardiol. 21 (suppl. III): S.29, 1989.
 561. Yin, F. C. P., G. S. Raizes, T. Guarnieri, H. A. Spurgeon, E. G. Lakatta, N. J. Fortuin, and M. L. Weisfeldt. Age‐associated decrease in ventricular response to haemodynamic stress during beta‐adrenergic blockade. Br. Heart J. 40: 1349–1355, 1978.
 562. Yin, F. C. P., H. A. Spurgeon, H. L. Greene, E. G. Lakatta, and M. L. Weisfeldt. Age‐associated decrease in heart rate response to isoproterenol in dogs. Mech. Ageing Dev. 10: 17–25, 1979.
 563. Yin, F. C. P., H. A. Spurgeon, and C. H. Kallman. Age‐associated alterations in viscoelastic properties of canine aortic strips. Circ. Res. 53: 464–472, 1983.
 564. Yin, F. C. P., H. A. Spurgeon, G. S. Raizes, H. L. Greene, M. L. Weisfeldt, and N. W. Shock. Age‐associated decrease in chrontropic response to isoproterenol [Abstract]. Circulation 4 (suppl. 2): 11–167, 1976.
 565. Yin, F. C. P., H. A. Spurgeon, K. Rakusan, M. L. Weisfeldt, and E. G. Lakatta. Use of tibial length to quantify cardiac hypertrophy: application in the aging rat. Am. J. Physiol. 243 (Heart Circ. Physiol. 14): H941–H947, 1982.
 566. Yin, F. C. P., H. A. Spurgeon, M. L. Weisfeldt, and E. G. Lakatta. Mechanical properties of myocardium from hyper‐trophied rat hearts. A comparison between hypertrophy induced by senescence and by aortic banding. Circ. Res. 46: 292–300, 1980.
 567. Yin, F. C. P., M. L. Weisfeldt, and W. R. Milnor. Role of aortic input impedance in the decreased cardiovascular response to exercise with aging in dogs. J. Clin. Invest. 68: 28–38, 1981.
 568. Young, J. B., J. W. Rowe, J. A. Pallotta, D. Sparrow, and L. Landsberg. Enhanced plasma norepinephrine response to upright posture and oral glucose administration in elderly human subjects. Metabolism 29: 532–539, 1980.
 569. Younis, L. T., J. A. Melin, A. R. Robert, and J. M. R. Detry. Influence of age and sex on left ventricular volumes and ejection fraction during upright exercise in normal subjects. Eur. Heart J. 11: 916–924, 1990.
 570. Yu, B. P., E. J. Masoro, and C. A. McMahan. Nutritional influences on aging of Fischer 344 rats: I. Physical, metabolic, and longevitiy characteristics. J. Gerontol. 40: 657–670, 1985.
 571. Ziman, B., H. A. Spurgeon, M. D. Stern, and E. G. Lakatta. A Ca2+ myofilament interaction modulates resting length of single rat ventricular myocytes [Abstract]. Circulation 82: III–214, 1990.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Edward G. Lakatta. Cardiovascular System. Compr Physiol 2011, Supplement 28: Handbook of Physiology, Aging: 413-474. First published in print 1995. doi: 10.1002/cphy.cp110117