S-nitrosocaptopril. I. Molecular characterization and effects on the vasculature and on platelets.
We have synthesized an S-nitrosylated derivative of captopril, S-nitrosocaptopril, that manifests nitrosovasodilatory activity, inhibits angiotensin converting enzyme activity and inhibits platelet aggregation. The direct vasodilatory effects of S-nitrosocaptopril reflect the effects of the thionitrite bond, the presence of which does not in any way influence S-nitrosocaptopril's ability to inhibit angiotensin converting enzyme. Thionitrite stimulation of both vascular and platelet soluble guanylate cyclase activity leads to increases in intracellular cyclic GMP that are accompanied by vasodilatation and platelet inhibition, respectively. S-nitrosocaptopril is a novel hybrid molecule that has potential use in the treatment of hypertension regardless of renin status, angina pectoris and congestive heart failure.
Loscalzo
J
J
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Smick
D
D
Andon
N
N
Cooke
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D010975:Platelet Aggregation Inhibitors; D051381:Rats; D014665:Vasodilator Agents
D000806:Angiotensin-Converting Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; C060039:S-nitrosocaptopril; D002216:Captopril