Angiotensin II inhibits the forearm vascular response to increased arterial pressure in humans

Objectives. This study tested the hypothesis that angiotensin II may inhibit the forearm vascular resistance response to an increase in arterial pressure in normal humans. Background. Angiotensin II inhibits baroreflex-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 pathophysiologic role of angiotensin II in hypertension and heart failure. Methods. Two investigations were performed. In the first, forearm vascular resistance responses were compared during equipressor infusions of angiotensin II and phenylephrine. In the second, heart rate, forearm vascular resistance and systemic venous norepinephrine spillover responses were compared during head-down tilt and head-down tilt plus phenylephrine with concomitant angiotensin II or vehicle infusions. Results. In the first study, forearm vascular resistance increased from 44 ± 12 (mean ± SD) to 54 ± 13 U (p < 0.05) during angiotensin II but did 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 decrease in heart rate and forearm vascular resistance during the combination of head-down tilt and phenylephrine were both attenuated during concomitant angiotensin II compared with vehicle infusions: ΔHR/ΔMAP = -2.2 beats/min per mm Hg during vehicle and -0.87 beats/min per mm Hg during angiotensin II (p = 0.07); ΔFVR/ΔMAP = -2.8 U/mm Hg during vehicle and -0.19 U/mm Hg during angiotensin II (p = 0.01), where ΔHR = change in heart rate; ΔMAP = change in mean arterial pressure; and ΔFVR = change in forearm vascular resistance. Norepinephrine spillover declined during vehicle infusions (612 ± 367 to 418 ± 196 ng/min, p < 0.05) but not during angiotensin II infusions despite a greater increase in mean arterial pressure when the subpressor angiotensin II was combined with head-down tilt and phenylephrine (6.0 ± 7.0 mm Hg during vehicle; 14 ± 9.4 mm Hg during angiotensin II, p < 0.01). Conclusions. Both pressor and nonpressor infusions of angiotensin II immediately inhibit the forearm vascular response to mild baroreflex loading in normal humans. If present over the long term, such effects could contribute to inappropriate peripheral resistance in diseases such as hypertension and congestive heart failure.