In vitro inhibition of human and rat platelets by NO donors, nitrosoglutathione, sodium nitroprusside and SIN-1, through activation of cGMP-independent pathways

GSNO exerts a potent antiaggregating power of platelets by cGMP-independent mechanisms that very plausibly are elicited by S-nitrosation (or nitrosylation) reactions. Extracellular RNSO (or NO donors metabolically converted to RSNO) may exchange with essential PSH (such as those of P2Y12, αIIbβ3, PDI of the platelet surface, or intracellular sGC and NSF, NEM Sensitive Factor) by S-nitrosation reactions: RSNO + PSH = PSNO + RSH (1). Since extracellular PSH and protein disulfides (PSSP) are supposed to be involved in complex SH/SS exchange reactions, functional to trigger platelet aggregation phenomena, the PSNO formation with essential PSH of the platelet surface, generated by GSNO by reaction (1), does not consent the platelet activation by thiol exchange reactions. The mixed action of SIN-1 and SNP are dependent on possible metabolism of SIN-1 and SNP to RSNO (GSNO) or NO. The central role exerted by essential PSH in platelet aggregation refers to the action of NEM and oxidants, known blockers of SH-dependent proteins.