S-nitrosocaptopril. II. Effects on vascular reactivity.
Experiments were designed to elucidate the effects of S-nitrosocaptopril (SnoCap) on vascular reactivity. Rings of bovine femoral and coronary arteries were mounted for isometric tension recording in physiological saline solution. SnoCap induced dose-dependent relaxations in both the coronary and femoral arteries, but inhibited contractions in the coronary artery to a significantly greater degree. Relaxations to SnoCap were inhibited by methylene blue. Angiotensin I and angiotensin II induced dose-dependent contractions in the bovine femoral artery. The angiotensin II antagonist saralasin induced comparable inhibition of the response to angiotensin I and angiotensin II. Captopril (10(-6) M) and SnoCap (10(-6) M) equally inhibited contraction to angiotensin I, inducing a 50-fold shift in the dose-response curve. SnoCap inhibited contraction to angiotensin II, inducing a 5-fold shift in the dose-response curve and depressing the maximum response. In summary, the S-nitrosylated derivative of captopril is a unique compound that inhibits vascular reactivity through activation of soluble guanylate cyclase and inhibition of angiotensin converting enzyme. This combined nitrovasodilator and angiotensin converting enzyme inhibitor may have clinical utility in hypertension, coronary artery disease and congestive heart failure.
Cooke
J P
JP
Division of Vascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Andon
N
N
Loscalzo
J
J
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects; D004347:Drug Interactions; D005263:Femoral Artery / Q000187:drug effects; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D012504:Saralasin / Q000494:pharmacology; D014665:Vasodilator Agents
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D000804:Angiotensin II; C060039:S-nitrosocaptopril; D000803:Angiotensin I; D002216:Captopril; D012504:Saralasin; D008751:Methylene Blue