[Inhibition of human platelet aggregation by a new class of soluble guanylate cyclase inhibitor, generating nitric oxide].

Diacetidine-di-N-oxide derivatives have been found to be capable of generating nitric oxide (NO) non-enzymatically, via an entirely new mechanism--NO splitting at physiological pH. The effects of the synthesized compounds on the human platelet soluble guanylate cyclase activity and ADP-induced human platelet aggregation have been investigated. Four out of seven derivatives tested exhibited a distinct correlation between the intensity of platelet guanylate cyclase activation, inhibition of platelet aggregation and acceleration of their disaggregation. The ability of the compounds to be decomposed under the given experimental conditions with NO formation and the observed correlation between the amount of the NO formed and the intensity of guanylate cyclase activation suggest that the NO-dependent mechanism of guanylate cyclase activation and the intraplatelet cGMP accumulation are responsible for the antiaggregating/disaggregating properties of the compounds used. The data obtained suggest that 1.2-diacetidine-di-N-oxide derivatives may be regarded as antiaggregating agents of a new class.