Central and peripheral effects of angiotensin II on the cardiovascular response to exercise

The authors tested the hypothesis that angiotensin II modulates cardiovascular responses to dynamic exercise via peripheral and central effects on the autonomic nervous system. Ten subjects performed three identical exercise tests during treatment with placebo, valsartan (an angiotensin II type 1 receptor blocker), or enalapril (an angiotensin-converting enzyme inhibitor). With placebo, plasma concentrations of angiotensin II, norepinephrine, and epinephrine were elevated during cycling at 80% of heart rate reserve (HRR). Enalapril attenuated increases in heart rate, mean arterial pressure (MAP), and catecholamines during cycling, whereas valsartan only attenuated MAP and rate-pressure product above 60% HRR, and norepinephrine. The different responses provoked by the two drug treatments suggest that angiotensin-converting enzyme inhibition affects cardiovascular responses to exercise by mechanisms unrelated to production of angiotensin II. Indices of autonomic function during dynamic exercise were not changed by either drug. Attenuation of norepinephrine release during exercise by valsartan suggests that angiotensin II facilitates the release of norepinephrine from sympathetic postganglionic neurons. Angiotensin II, therefore, contributes to the pressor response to exercise by inducing peripheral vasoconstriction and facilitation of norepinephrine release from postganglionic sympathetic nerve endings that are unrelated to central activation of the autonomic nervous system.