Resveratrol inhibits Ca(2+) signals and aggregation of platelets

BACKGROUND: Resveratrol has been shown to inhibit platelet aggregation. However, the mechanism for this action of resveratrol remains to be clarified. The purpose of this study was to elucidate the Ca(2+)-related mechanism for the inhibitory action of resveratrol on platelet aggregation. METHODS: Ca(2+) entry and subsequent aggregation of human platelets induced by different stimulants including thrombin, thapsigargin, and 1-oleoyl-2-acetylglycerol (OAG) were measured by the fluorescence method and light transmittance method, respectively. Each stimulant was added to a nominally Ca(2+)-free medium containing platelets, and then CaCl(2) was added to the medium to induce Ca(2+) influx into platelets. RESULTS: Thapsigargin-induced Ca(2+) entry into platelets and subsequent platelet aggregation were significantly inhibited in the presence of resveratrol at 6.25 μM or higher concentrations, while OAG-induced Ca(2+) entry and subsequent platelet aggregation were not affected by resveratrol at concentrations up to 50 μM. In the nominally Ca(2+)-free medium, thrombin induced a small transient increase in intracellular Ca(2+) concentrations, which was attenuated in the presence of resveratrol at 12.5 μM or higher concentrations. Thrombin-induced Ca(2+) entry into platelets and subsequent platelet aggregation were significantly inhibited in the presence of resveratrol at 12.5 μM or higher concentrations. CONCLUSIONS: The results suggest that resveratrol inhibits thrombin-induced platelet aggregation through decreasing Ca(2+) release from its stores and inhibiting store-operated Ca(2+) influx into platelets.