[Mechanism of the vasodilating effect and blood platelet- antiaggregating activity of molsidomine and SIN-1].
Present evidence indicates that the active metabolite SIN-1 of the prodrug molsidomine dilates vascular smooth muscle and inhibits platelet aggregation by a direct stimulatory effect on soluble guanylate-cyclase in the cytosol of vascular smooth muscle cells and platelets, respectively. Evidence from studies in bovine coronary arteries is presented to proof the causal relation between SIN-1 induced rises in cGMP and relaxation under a variety of pharmacological conditions. In contrast to organic nitrates, SIN-1, which activates guanylate-cyclase in vitro independently of the presence of added cysteine, does not cause tolerance. Tolerance most pronounced with nitroglycerin appears to be due to a direct inactivating effect of this drug on guanylate-cyclase.
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009566:Nitrates / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D009566:Nitrates; C002385:linsidomine; D008981:Molsidomine; D006152:Cyclic GMP
Mécanisme de l'effet vasodilatateur et de l'action anti-agrégante plaquettaire de la molsidomine et du SIN-1.