Platelet cyclic GMP levels in unstable angina and myocardial infarction

Background: Several studies showed that there is a state of platelet hyperactivaction in patients with coronary syndrome: the aim of this study is to investigate if the platelet nitric oxide-cyclicGMP (NO-cGMP) pathway, that regulates platelet aggregation is altered in patients with unstable angina (UA) and acute myocardial infarction (AMI). Methods and results: Population included 11 patients with UA, 12 patients with AMI and 23 controls. Platelet cGMP was measured by a radioimmunoassay kit, under basal conditions and after stimulation with sodium nitroprusside (SNP), which maximally stimulates soluble guanylate cyclase (sGC), used as an indirect measurement of active sGC. Basal platelet cGMP values were significantly (P<0.001) higher in patients with UA and AMI than in controls (UA, 1089 +/- 412 pmol/10(10) platelets; AMI, 1071 +/- 507 pmol/10(10) platelets; controls, 492 +/- 201 pmol/10(10) platelets). The final cGMP level reached after SNP stimulation was significantly more elevated in UA, compared with both AMI (P<0.05) and controls (P<0.02) (UA, 4428 +/- 2723 pmol/10(10) platelets; AMI, 2728 +/- 655 pmol/10(10) platelets; controls, 2772 +/- 1031 pmol/10(10) platelets); on the contrary no significant difference between AMI and controls was observed. Conclusions: Basal platelet cGMP is significantly higher in both UA and AMI groups. This observation suggests that: (1) platelet-derived NO synthesis may be enhanced inUA and AMI, due to increase of intraplatelet calcium level and of platelet cNOS activation; (2) platelets from UA and AMI patients are continuously stimulated by the high-level NO production due to increased iNOS expression. As far as SNP-dependent cGMP production is concerned, UA and AMI behave as two separate conditions. SNP-stimulated activity in UA is higher than in controls, while a loss of functional sGC is observed in AMI.