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

摘要: Three different NO donors, S-nitrosoglutathione (GSNO), sodium nitroprusside (SNP) and 3-morpholino-sydnonimine hydrochloride (SIN-1) were used in order to investigate mechanisms of platelet inhibition through cGMP-dependent -independent pathways both human rat. To this purpose, we also evaluated what extent cGMP-independent related with the entity release from each drug. SNP, GSNO SIN-1 (100 μM) effects on aggregation, presence or absence a soluble guanylate cyclase inhibitor (ODQ), fibrinogen receptor (α(IIb)β(3)) binding specific antibody (PAC-1), donors rat rich plasma (PRP) measured. Inhibition aggregation (induced by ADP) resulted be greater than was most powerful (IC(50) values, μM): (a) human, GSNO=0.52±0.09, SNP=2.83 ± 0.53, SIN-1=2.98 1.06; (b) rat, = 28.4 6.9, SNP 265 73, SIN-1=108 85. action species mediated characterized highest PRP. displayed mixed (cGMP-dependent independent), except for (cGMP-dependent), respectively lower nearly absent delivery. Conversely, all NO-donors prevalently inhibited PAC-1 α(IIb)β(3) pathways. A modest relationship between responses found. Interestingly, difference mechanism attributed S-nitrosylation non-essential essential protein SH groups.