Glyceryl trinitrate and platelet aggregation: effects of N-acetyl-cysteine

The concentration range of GTN causing inhibition of platelet aggregation in vitro is much higher than the plasma concentrations achieved clinically. This action is potentiated by the sulphydryl donor N-acetylcysteine. We have investigated the effects of GTN given with and without N-acetylcysteine on ex vivo platelet aggregation in man. In a double-blind randomised crossover trial eight healthy volunteers were treated with 20 mg of transdermal GTN/24 h, together with N-acetylcysteine 200 mg three times daily or matching placebo. Platelet aggregation, measured ex vivo by whole blood impedance aggregometry in response to adenosine diphosphate, was not significantly altered by GTN acutely or after 4 days' treatment with or without N-acetylcysteine. Platelet cyclic guanosine monophosphate levels were not significantly altered by GTN either in the absence or presence of N-acetylcysteine. This result implies that previously reported beneficial effects of GTN in myocardial infarction or unstable angina are unlikely to be attributable to direct pharmacological inhibition of platelet aggregation.