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 sympathetic nervous system. We compared the effect of local brachial artery infusions of an ACE inhibitor (perindoprilat) with the effect of placebo (0.9% NaCl) on endogenously mediated (lower body negative pressure [LBNP]) and exogenously mediated (brachial artery infusions of norepinephrine) sympathetic vasoconstriction.


RESULTS
Eight healthy, normotensive male volunteers (20 to 32 years) were studied on one occasion. Forearm blood flow (FABF; mL x dL forearm(-1) x min(-1)) responses to LBNP (-20 cm H2O) and increasing increments of norepinephrine (60, 120, and 240 pmol/min) were compared when coinfused with placebo and perindoprilat (5 nmol/mL). FABF was measured simultaneously in both arms by venous occlusion plethysmography with mercury-in-Silastic strain gauges with drugs infused locally at the left brachial artery. The right arm served as a control. Baseline FABFs did not differ between the infused and control arms (3.04+/-0.52 versus 3.05+/-0.42 mL x dL forearm(-1) x min(-1); P=.98). Perindoprilat did not alter FABF when infused alone, but the FABF response to LBNP in the infused arm was attenuated during the perindoprilat infusion compared with placebo (-17.8+/-4.3% versus -33.8+/-3.1%, respectively; P=.015). The FABF response to the maximum dose of norepinephrine was also attenuated during the perindoprilat infusion compared with placebo (-28.3+/-1.4% versus -36.9+/-2.8%, respectively; P=.015). The mean slope of the FABF (log transformed) versus norepinephrine dose-response curve was significantly attenuated by perindoprilat compared with placebo (-0.11+/-0.019 versus -0.02+/-0.02; P=.001).


CONCLUSIONS
We conclude that ACE inhibition has a significant postsynaptic sympatholytic effect in the forearm circulation of men.
Lyons
D
D
Clinical Age Research Unit, King's College School of Medicine and Dentistry, London, UK. d.lyons@kcl.ac.uk
Roy
S
S
O'Byrne
S
S
Swift
C G
CG
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects; D004338:Drug Combinations; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D008150:Lower Body Negative Pressure; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010919:Placebos / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D014655:Vascular Resistance; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004338:Drug Combinations; D007211:Indoles; D010919:Placebos; D014662:Vasoconstrictor Agents; C053500:perindoprilat; D009638:Norepinephrine