Comparison of angiotensin-converting enzyme inhibitors in the rat in perfused hindlimbs and in vivo.
To investigate the role of local renin angiotensin systems in the functional responses to angiotensin I and II, the effects of angiotensin I and angiotensin II on resistance were measured in perfused hindlimbs of rats under normal conditions and during infusion of enalaprilate, lisinopril, zabiciprilate and captopril at two infusion rates. The angiotensin-converting enzyme (ACE) inhibitors significantly increased ED50 and decreased maximal resistance changes of angiotensin I dose dependently, without effects on angiotensin II responses. Captopril increased the ED50 of angiotensin I significantly more than did the other ACE inhibitors at a low infusion rate. The ACE inhibitors, except for lisinopril, increased the ED50 of angiotensin I pressor responses in vivo to the same extent, and were similarly potent to inhibit plasma ACE activity at 15 min after injection. The ratio of the doses of the ACE inhibitors used in vivo was the same as in perfused hindlimbs. These results suggest that, in the hindlimbs, angiotensin I causes ACE-dependent vasoconstriction. Captopril may be more effective to inhibit local ACE than the other ACE inhibitors investigated.
Nelissen-Vrancken
M H
MH
Department of Pharmacology, University of Limburg, Maastricht, Netherlands.
Leenders
P J
PJ
Bost
J G
JG
Struijker-Boudier
H A
HA
Smits
J F
JF
D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply*; D017706:Lisinopril; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A