The hemodynamic effects of S-nitrosocaptopril in anesthetized dogs.
We studied the effects of a unique vasoactive agent, S-nitrosocaptopril (SnoCap), in an anesthetized canine preparation. We have previously demonstrated that this agent manifests the properties of both a direct nitrovasodilator and an angiotensin-converting enzyme inhibitor in vitro. The present investigation was performed to evaluate the effects of SnoCap in vivo. Intravenous administration of SnoCap produced immediate reductions in blood pressure and significantly attenuated the pressor response to angiotensin I. Equieffective doses of SnoCap had a greater duration of action after intravenous bolus administration compared with nitroglycerin (15.3 +/- 2.6 min vs. 3.2 +/- 0.5 min, respectively; P less than .01); importantly, this effect was apparent despite the relatively short plasma half-life of the compound (T1/2 alpha = 0.48 min, T1/2 beta = 5.54 min) and did not appear to be the result of inhibition of angiotensin-converting enzyme. Another unexpected property of SnoCap was that its nitrovasodilator effect was 10- to 30-fold less potent than nitroglycerin when administered as a bolus, but more efficacious when given by continuous infusion. These data support the view that SnoCap is a vasoactive substance with the properties of a nitrovasodilator and an angiotensin-converting enzyme inhibitor, as well as the unique properties of an extended duration of action and greater potency when administered by continuous intravenous infusion than by bolus injection. The clinical utility of this compound in humans and in individuals with specific disease states remains to be demonstrated.
Shaffer
J E
JE
Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts.
Lee
F
F
Thomson
S
S
Han
B J
BJ
Cooke
J P
JP
Loscalzo
J
J
D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D004285:Dogs; D004361:Drug Tolerance; D005260:Female; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; C060039:S-nitrosocaptopril; D000803:Angiotensin I; D002216:Captopril; D005996:Nitroglycerin