Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release

Background - Moderate red wine consumption is inversely associated with cor onary ischemia, and both red wine and purple grape juice (PGJ) contain flav onoids with antioxidant and antiplatelet properties believed to be protecti ve against cardiovascular events. Acute cardiac events are also associated with decreased platelet-derived nitric oxide (NO) release. In this study, t he effects of PGJ and PGJ-derived flavonoids on platelet function and plate let NO production were determined. Methods and Results - Incubation of platelets with dilute PGJ led to inhibi tion of aggregation, enhanced release of platelet-derived NO, and decreased superoxide production. To confirm the in vivo relevance of these findings, 20 healthy subjects consumed 7 mt kg(-1) d(-1) of PGJ for 14 days. Platele t aggregation was inhibited after PGJ supplementation, platelet-derived NO production increased from 3.5 +/-1.2 to 6.0 +/-1.5 pmol/10(8) platelets, an d superoxide release decreased from 29.5 +/-5.0 to 19.2 +/-3.1 arbitrary un its (P <0.007 and P <0.05, respectively), alpha -Tocopherol levels increase d significantly after PGJ consumption (from 15.6 +/-0.7 to 17.6 +/-0.9 mu m ol/L; P <0.009), and the plasma protein-independent antioxidant activity in creased by 50.0% (P <0.05). Last, incubation of platelets with select flavo noid fractions isolated from PGJ consistently attenuated superoxide levels but had variable effects on whole-blood aggregation, platelet aggregation, and NO release. Conclusions - Both in vitro incubation and oral supplementation with PGJ de crease platelet aggregation, increase platelet-derived NO release, and decr ease superoxide production. These findings may be a result of antioxidant-s paring and/or direct effects of select flavonoids found in PGJ. The suppres sion of platelet-mediated thrombosis represents a potential mechanism for t he beneficial effects of purple grape products, independent of alcohol cons umption, in cardiovascular disease.