The effects of S-nitrosocaptopril on canine coronary circulation.
Nitroglycerin (NTG) has been used for more than a century for the relief of angina pectoris and is regarded as an extrinsic donor of nitric oxide (NO). Captopril, an angiotensin-converting enzyme inhibitor (ACEI), is reported to have beneficial effects on survival in acute myocardial infarction. In this study, a hybrid compound of NO and ACEI, S-nitrosocaptopril (S-NO-Cap), was synthesized, which was characterized by its molecular structure. Its coronary effects in chronically instrumented dogs were compared with those of NTG and captopril. S-NO-Cap (50 micrograms/kg i.v.) increased epicardial coronary diameter (CoD) by a maximum of 5.2% for more than 20 min. NTG (15 micrograms/kg i.v.) increased CoD by a maximum of 4.6% for 10 min, i.e., the effect was equipotent with that of S-NO-Cap (50 micrograms/kg i.v.). However, S-NO-Cap produced its maximal CoD increase more slowly than NTG did. Both S-NO-Cap and NTG transiently increased coronary blood flow. However, NTG had a more potent effect than S-NO-Cap (28.4 vs. 40.8 ml/min, respectively). Captopril, on the other hand, had almost no effect on either CoD or coronary blood flow. Thus, the vasodilatory action of S-NO-Cap more closely resembled that of NTG than that of captopril. Therefore, S-NO-Cap may dilate coronary arteries by virtue of its NO moiety rather than by its ACEI properties. These findings indicate that S-NO-Cap is a potential antianginal drug.
Nakae
I
I
First Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
Takahashi
M
M
Kinoshita
T
T
Matsumoto
T
T
Kinoshita
M
M
D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; C060039:S-nitrosocaptopril; D002216:Captopril