The influence of antiplatelet therapy on the in vivo nitric oxide bioavailability

2012 
Introduction Antiplatelet therapy in large focuses on the efficiency of inhibition of platelet aggregation. Relatively little is known about the short- and long-term influence of antiplatelet drugs on the function of vascular endothelium, including their effects on NO metabolism in patients. This study demonstrates the profile of NO metabolites and how it correlates with different levels of cGMP and the antioxidant status in plasma in patients receiving clopidogrel. Methods 52 CAD patients receiving clopidogrel were recruited into the study. In the clopidogrel naive group (30 subjects) the blood was taken before and 2 h after receiving a standard loading dose of clopidogrel (600 mg). In the clopidogrel chronic group (22 subjects) the blood was taken after at least 2 months of being on a maintenance dose (75 mg). All plasma samples were measured for NO metabolites, cGMP and ORAC index. Results In the acute setting, nitrite was increased from 157.1 ± 82.4 to 194.2 ± 87.64 nM ( p  = 0.0674), as well as cGMP from 214.2 ± 124.4 to 231.5 ± 107.8 pmol/ml ( p  = 0.0586) and ORAC index from 60.66 ± 11.45 to 64.15 ± 10.61% ( p  = 0.0372). In the chronic setting, nitrite was increased from 157.1 ± 82.4 to 254.3 ± 139.4 nM ( p  = 0.0028), as well as cGMP from 214.2 ± 124.4 to 276.9 ± 72.15 pmol/ml ( p  = 0.0519). In both acute and chronic groups RSNO did not change. Conclusions Patients receiving short- or long-term clopidogrel exhibit a time-proportional increase in NO bioavailability and effective vasodilation, as reflected by higher levels of nitrite and cGMP. The increased ORAC index in the acute group also suggests a parallel positive influence on the total antioxidant capacity of plasma.
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