Inhibition of platelet aggregation by S-nitroso-cysteine via cGMP-independent mechanisms:: evidence of inhibition of thromboxane A2 synthesis in human blood platelets

S-Nitroso-cysteine (SNC), a putative endothelium-derived relating factor, potently inhibited collagen- and arachidonic acid-induced platelet aggregation (IC50 = 100 nM) and thromboxane A(2) (TxA(2)) synthesis of human blood platelets, ODQ, a selective inhibitor of the soluble guanylyl cyclase, inhibited SNC-induced formation of cGMP but did not reverse inhibition by SNC of collagen- and arachidonic acid-induced platelet aggregation, Combination of ODQ with SQ-29548, a specific platelet TxA(2) receptor antagonist, did not modify the antiaggregatory action of SNC. Our study shows that SNC inhibits platelet aggregation by cGMP-independent mechanisms that may involve inhibition of TxA(2) synthesis in human platelets, (C) 1999 Federation of European Biochemical Societies.