EFFECT OF A PRESSOR INFUSION OF ANGIOTENSIN-II ON SYMPATHETIC ACTIVITY AND HEART-RATE IN NORMAL HUMANS

We tested the hypothesis that pressor infusions of angiotensin II (AII) could stimulate the sympathetic nervous system as reflected by norepinephrine (NE) spillover in humans. AII 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 AII, vehicle, or phenylephrine in the supine position and then after 15 minutes of head-up and 15 minutes of head-down tilt. Both AII 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 AII 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 AII 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 AII cannot be attributed to global sympathetic stimulation. This suggests that AII may inhibit the efferent response to acute baroreceptor loading in humans.