Clopidogrel results in favourable changes in nitric oxide metabolism in patients undergoing percutaneous coronary intervention

Abstract

Clopidogrel has been shown to have a morbidity and mortality benefit in the prevention of ischaemic complications in patients with acute coronary syndrome and/or after percutaneous coronary intervention (PCI)1. 600mg of clopidogrel can not only significantly inhibit platelet inhibition acutely (within 2 hours) but also improve endothelial dysfunction in stable CAD patients via a mechanism independent of platelet function2. A reduction in endothelial injury after PCI also occurs in the presence of clopidogrel3. Clopidogrel has also been associated with improved systemic endothelial nitric oxide (NO) bioavailability in patients with coronary artery disease2. Endothelial nitric oxide synthase (eNOS) is the main source of NO in the vasculature4 and its activity directly proportional to plasma nitrite concentration and reflects cardiovascular NO bioavailability5. 70% of resting plasma nitrite is derived from eNOS activity in humans. NO metabolites including nitrite, nitrate and RSNO are now considered a direct measure of a physiological activity of NO and also a biologically active NO reservoir. We examined the effect of acute and chronic clopidogrel on these NO metabolites, the vasodilatory effect (cGMP) and oxidative/nitrosative stress markers in the plasma in patients undergoing PCI