Evidence for the inhibitory role of guanosine 3', 5'-monophosphate in ADP-induced human platelet aggregation in the presence of nitric oxide and related vasodilators.

Previous observations that platelet guanosine 3’. 5’-monophosphate (cyclic GMP) accumulation occurred during platelet aggregation and also in the presence of nitroprusside. which inhibits aggregation. prompted an evaluation of the effects of nitroprusside. nitric oxide. and related agents on human platelet aggregation. Adenosine diphosphate (ADP) was employed to induce irreversible aggregation of human platelets in platelet-rich plasma. Nitroprusside. nitric oxide. and N-methyl-N’-nitro-N-nitrosoguanidine. in a concentration-dependent manner. inhibited ADPinduced platelet aggregation. markedly activated soluble platelet guanylate cyclase (70-280-fold). and markedly elevated platelet cyclic GMP levels (100-200-fold). The gaseous phase of cigarette smoke. which contains nitric oxide. also inhibited platelet aggregation and elevated platelet cyclic GMP levels. In addition to attenuating aggregation. these agents were effective in disaggregating platelets. which was associated with a concomitant rise in