ANGIOTENSIN-II INHIBITS THE FOREARM VASCULAR-RESPONSE TO INCREASED ARTERIAL-PRESSURE IN HUMANS

Objectives. This study tested the hypothesis that angiotensin II may i nhibit the forearm vascular resistance response to an increase in arte rial pressure in normal humans. Background. Angiotensin II inhibits ba roreflex-mediated reductions in heart rate and peripheral sympathetic activity during increases in arterial pressure in experimental animals . If present in humans, such effects could contribute to the pathophys iologic role of angiotensin II in hypertension and heart failure. Meth ods. Two investigations were performed. In the first, forearm vascular resistance responses were compared during equipressor infusions of an giotensin II and phenylephrine. In the second, heart rate, forearm vas cular resistance and systemic venous norepinephrine spillover response s were compared during head-down tilt and head-down tilt plus phenylep hrine with concomitant angiotensin II or vehicle infusions. Results. I n the first study, forearm vascular resistance increased from 44 +/- 1 2 (mean +/- SD) to 54 +/- 13 U (p < 0.05) during angiotensin II but di d not change during phenylephrine infusions (39 +/- 8.5 to 40 +/- 14 U ) that increased mean arterial pressure comparably (88 +/- 9.8 to 103 +/- 14 mm Hg during angiotensin II, p < 0.001; 91 +/- 7.6 to 104 +/- 9 .2 mm Hg during phenylephrine, p < 0.001). In the second study, the de crease in heart rate and forearm vascular resistance during the combin ation of head-down tilt and phenylephrine were both attenuated during concomitant angiotensin II compared with vehicle infusions: Delta HR/M AP = -2.2 beats/min per mm Hg during vehicle and -0.87 beats/min per m m Bg during angiotensin II (p = 0.07); Delta FVR/Delta MAP = -2.8 U/mm Hg during vehicle and -0.19 U/mm Hg during angiotensin II (p 0.01), w here Delta HR = change in heart rate; Delta MAP = change in mean arter ial pressure; and Delta FVR = change in forearm vascular resistance. N orepinephrine spillover declined during vehicle infusions (612 +/- 367 to 418 +/- 196 ng/min, p < 0.05) but not during angiotensin II infusi ons despite a greater increase in mean arterial pressure when the subp ressor angiotensin II was combined with head-down tilt and phenylephri ne (6.0 +/- 7.0 mm Hg during vehicle; 14 +/- 9.4 mm Hg during angioten sin II, p < 0.01). Conclusions. Both presser and nonpressor infusions of angiotensin II immediately inhibit the forearm vascular response to mild baroreflex loading in normal humans. If present over the long te rm, such effects could contribute to inappropriate peripheral resistan ce in diseases such as hypertension and congestive heart failure.