The autonomic adjustments to exercise in humans (i.e., tachycardia and vasoconstriction) are thought to be mediated by two primary signals (mechanisms): central command and feedback from group III and IV muscle afferents with mechano- and chemosensitive endings. Recent findings suggest that chemosensitive muscle afferents (i.e., activation of muscle chemoreflexes) may selectively mediate vasoconstriction via increases in efferent sympathetic nerve activity (SNA) whereas central command and/or mechanosensitive muscle afferents may selectively mediate tachycardia via withdrawal of cardiac vagal activity. Furthermore, indirect evidence suggests that the arterial and cardiopulmonary baroreflexes may modulate (inhibit) increases in SNA during exercise. Finally, although the mode and intensity of exercise are known to be primary determinants of the magnitude of increase in SNA, indirect evidence suggests that the duration of the exercise (muscle fatigue), the size of the contracting muscle mass, the state of conditioning, and the age of the subject could also importantly influence the sympathetic response.
The aims of the present proposal will be to: (1) determine the influence of muscle chemoreflexes on SNA during exercise; (2) determine whether arterial and/or cardiopulmonary baroreflexes modulate SNA during exercise, and (3) determine whether the above-mentioned factors (i.e., exercise duration, muscle mass, etc.) are important determinants of the SNA response to exercise. To achieve these aims, direct, intraneural recordings of SNA (microneurography) to non-contracting muscle in the leg (peroneal nerve) during handgrip or contralateral leg exercise will be combined with several unique experimental paradigms that are designed to isolate the mechanism or putative determinant in question. Other measurements will include arterial blood pressure (sphygmomanometry), contracting muscle EMG activity (index of central command), post-exercise hyperemia (venous occlusion plethysmography; index of muscle chemoreflex stimulation), heart rate (ECG), and ventilation (pneumotachometer). Sinusoidally-applied neck pressure and low levels (-10 mmHg) of lower body negative pressure will be used to isolate the potential modulatory effects of carotid and cardiopulmonary baroreflexes, respectively. In nine of the ten proposed studies, healthy men and women aged 18-34 yr will be studied; in one study, rigorously screened, healthy older (55-65 yr) men and women will be studied to determine the effects of age on the SNA response to exercise. The results of these studies should provide new and useful information on the mechanisms which regulate the sympathetic nerve responses to exercise in healthy humans and, thus, provide a fundamental basis from which to study possible altered regulation in such pathophysiological states as congestive heart failure, hypertension, and autonomic neuropathy.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Respiratory and Applied Physiology Study Section (RAP)
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University of Arizona
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Seals, Douglas R (2003) Habitual exercise and the age-associated decline in large artery compliance. Exerc Sport Sci Rev 31:68-72
Jones, Pamela Parker; Shapiro, Linda F; Keisling, Gretchen A et al. (2002) Is autonomic support of arterial blood pressure related to habitual exercise status in healthy men? J Physiol 540:701-6
Clevenger, Christopher M; Parker Jones, Pamela; Tanaka, Hirofumi et al. (2002) Decline in insulin action with age in endurance-trained humans. J Appl Physiol 93:2105-11
Bell, C; Seals, D R; Monroe, M B et al. (2001) Tonic sympathetic support of metabolic rate is attenuated with age, sedentary lifestyle, and female sex in healthy adults. J Clin Endocrinol Metab 86:4440-4
Jones, P P; Shapiro, L F; Keisling, G A et al. (2001) Altered autonomic support of arterial blood pressure with age in healthy men. Circulation 104:2424-9
van Pelt, R E; Dinneno, F A; Seals, D R et al. (2001) Age-related decline in RMR in physically active men: relation to exercise volume and energy intake. Am J Physiol Endocrinol Metab 281:E633-9
Schiller, B C; Casas, Y G; Desouza, C A et al. (2001) Maximal aerobic capacity across age in healthy Hispanic and Caucasian women. J Appl Physiol 91:1048-54
Monroe, M B; Seals, D R; Shapiro, L F et al. (2001) Direct evidence for tonic sympathetic support of resting metabolic rate in healthy adult humans. Am J Physiol Endocrinol Metab 280:E740-4
Dinenno, F A; Jones, P P; Seals, D R et al. (2000) Age-associated arterial wall thickening is related to elevations in sympathetic activity in healthy humans. Am J Physiol Heart Circ Physiol 278:H1205-10
Jones, P P; Davy, K P; Seals, D R (1999) Influence of gender on the sympathetic neural adjustments to alterations in systemic oxygen levels in humans. Clin Physiol 19:153-60

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