Effect of a pressor infusion of angiotensin II on sympathetic activity and heart rate in normal humans.

Abstract

We tested the hypothesis that pressor infusions of angiotensin II (All) could stimulate the sympathetic nervous system as reflected by norepinephrine (NE) spillover in humans. AlI was infused at 5 ng/kg/min in six healthy volunteers, with vehicle and phenylephrine infusions as controls, on 3 separate days. Heart rate, mean arterial pressure, plasma NE, NE clearance, and NE spillover were assessed before and after 30-minute infusions of All, vehicle, or phenylephrine in the supine position and then after 15 minutes of head-up and 15 minutes of head-down tilt. Both All and phenylephrine raised mean arterial pressure (88+±9.6 to 103±+14 mm Hg, p <0.001, and 91±7.6 to 104±9.2 mm Hg, p <0.001, respectively), whereas heart rate fell only with phenylephrine (60±6 to 51± 6.3 beats/min,p<0.001). Neither plasma NE nor NE spillover was affected by either infusion, and NE clearance declined slightly with both. No changes occurred in any variable during vehicle infusions in the supine position. During upright tilt, NE spillover increases were attenuated by both All and phenylephrine while NE clearance changes were slightly greater, leaving plasma NE increases similar on each day. During head-down tilt, NE and NE spillover declined comparably on each study day. We conclude that in healthy humans, using NE spillover as the measure, 1) pressor infusions of All do not increase basal sympathetic activity, enhance sympathetic stimulation during baroreceptor unloading (upright tilt), or attenuate sympathetic inhibition during baroreceptor loading (head-down tilt) and 2) the absence of bradycardia during pressor infusions of All cannot be attributed to global sympathetic stimulation. This suggests that All may inhibit the efferent response to acute baroreceptor loading in humans. (Circulation Research 1991;68:263-268) T he peptide angiotensin II (All), apart from its direct effect, a potent pressor action, has powerful and diverse indirect effects on cardiovascular regulation.' These effects reportedly include activation of the sympathetic nervous system at central, ganglionic, and peripheral sites2-4; potentiation of the vasopressor action of norepinephrine (NE)5-7; and central inhibition of the sinoaortic baroreflex.8-10 Most data regarding these indirect effects of All have been gathered in animal studies; relatively little information has come from human investigation. At the same time, the success of angiotensin-converting enzyme inhibitor therapy for both hypertension and heart failure has focused attention on the need for a better understanding of the overall effect of All on the human circulation, because the mechanisms by which these drugs produce sustained clinical benefit are not yet fully clear.In this study, we investigated the possibility that pressor levels of All might stimulate the sympathetic nervous system in normal humans, either at rest or in response to maneuvers that increase and decrease basal sympathetic tone. We also investigated whether the previously observed failure of pressor infusions of All to caus...

Angiotensin II exerts differential actions on renal nerve activity and heart rate.

“…The curve relating RSNA to MAP during infusions of graded doses of Ang II was identical to that during infusions of graded doses of phenylephrine, suggesting that the Ang II-induced reduction in RSNA was simply a reflex response to the increase in arterial pressure. Although it has been reported that the activity of the sympathetic nervous system did not increase during Ang II infusion in humans as assessed by measurement of norepinephrine spillover 19 or renal norepinephrine release, 20 the present results provide direct evidence that Ang II does not increase RSNA. Indeed, the results indicate that the pressor response to Ang II is buffered by a decrease in RSNA.…”

Effect of Low-Density Lipoprotein Cholesterol on Angiotensin II Sensitivity

“…13,20 It is caused by a centrally mediated inhibitory effect of Ang II on the response to baroreflex activation and not to an Ang IImediated increase in sympathetic tone. 21,22 If this inhibitory effect on baroreflex activation had not occurred, the blood pressure dose-response curve to Ang II with the infusion rates applied would have been lower and likely comparable to that of norepinephrine.…”

Interactions between the sympathetic nervous system and the RAAS in heart failure

“…Presynaptic facilitation of norepinephrine release has been demonstrated in the normal human forearm circulation at very high concentrations of angiotensin II [24] but not in normal humans undergoing mild to moderate degrees of sympathostimulation during decreased central venous volume, nor has it been demonstrated in patients with heart failure with high baseline sympathetic tone [25][26][27][28]. However, a physiologic role for angiotensin II as an inhibitor of normal baroreflexmediated reduction in heart rate and sympathetic activity has been demonstrated in normal humans and animals [29,30]. Interesting recent work regarding the cardiocardiac sympathetic reflex in animals with experimental heart failure also has linked angiotensin II to the activation of the SNS, which occurs with chemical or mechanical stimulus to the left ventricular myocardium [22,23].…”