ACE-INHIBITION - POSTSYNAPTIC ADRENERGIC SYMPATHOLYTIC ACTION IN MEN

Background The mechanisms by which ACE inhibitors produce a sustained clinical benefit are not entirely clear but may involve the sympatheti c nervous system. We compared the effect of local brachial artery infu sions of an ACE inhibitor (perindoprilat) with the effect of placebo ( 0.9% NaCl) on endogenously mediated (lower body negative pressure [LBN P]) and exogenously mediated (brachial artery infusions of norepinephr ine) sympathetic vasoconstriction. Methods and Results Eight healthy, normotensive male volunteers (20 to 32 years) were studied on one occa sion. Forearm blood flow (FABF; mL.dL forearm(-1).min(-1)) responses t o LBNP (-20 cm H2O) and increasing increments of norepinephrine (60, 1 20, and 240 pmol/min) were compared when coinfused with placebo and pe rindoprilat (5 nmol/ml). FABF was measured simultaneously in both arms by venous occlusion plethysmography with mercury-in-Silastic strain g auges with drugs infused locally at the left brachial artery. The righ t arm served as a control. Baseline FABFs did not differ between the i nfused and control arms (3.04+/-0.52 versus 3.05+/-0.42 mL.dL forearm( -1).min(-1); P=.98). Perindoprilat did not alter FABF when infused alo ne, but the FABF response to LBNP in the infused arm was attenuated du ring the perindoprilat infusion compared with placebo (-17.8+/-4.3% ve rsus -33.8+/-3.1%, respectively; P=.015). The FABF response to the max imum dose of norepinephrine was also attenuated during the perindopril at infusion compared with placebo (-28.3+/-1.4% Versus -36.9+/-2.8%, r espectively; P=.015). The mean slope of the FABF (log transformed) ver sus norepinephrine dose-response curve; was significantly attenuated b y perindoprilat compared with placebo (-0.11+/-0.019 versus -0.02+/-0. 02; P=.001). Conclusions We conclude that ACE inhibition has a signifi cant postsynaptic sympatholytic effect in the forearm circulation of m en.