Regulation of regional vascular tone: the role of angiotensin conversion in human forearm resistance vessels.
Inhibition of the action of endothelially-located angiotensin converting enzyme (ACE) in blood vessels of the human forearm was studied using enalaprilat, the active metabolite of the prodrug enalapril. In a dose of 5 micrograms/min enalaprilat inhibits arteriolar vasoconstriction in response to angiotensin I (Ang I) and enhances vasodilation in response to bradykinin. At this dose enalaprilat had no effect on resting forearm blood flow, or on the reduction in forearm blood flow in response to application of lower body negative pressure, in subjects with normal sodium intake. Following sodium depletion, however, enalaprilat produced an increase in resting forearm blood flow compared with the response in the same subjects under normal-sodium conditions. It appears that local ACE within forearm resistance vessels of healthy volunteers is unlikely to play an important role in regulation of local vascular tone in the sodium-replete state. However, in sodium-depleted subjects, and perhaps also in other circumstances where circulating concentrations of Ang I are elevated, local ACE may significantly affect vascular tone.
Webb
D J
DJ
Department of Pharmacology, St. George's Hospital Medical School, London, UK.
Collier
J G
JG
Seidelin
P H
PH
Struthers
A D
AD
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001808:Blood Vessels / Q000201:enzymology*; D004039:Diet, Sodium-Restricted; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008150:Lower Body Negative Pressure; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat