Resveratrol, at Concentrations Attainable with Moderate Wine Consumption, Stimulates Human Platelet Nitric Oxide Production3

Abstract

The mechanisms through which moderate wine consumption reduces ischemic cardiovascular events are not yet fully unraveled. Grape extracts or a mixture of the polyphenols contained in wine were previously shown to increase nitric oxide (NO); however, little information is available on the effect of resveratrol, one of the main polyphenols of wine, on platelet NO production. We assessed the effects of resveratrol, at the concentrations attainable after moderate wine intake, on platelet NO production and the mechanism of this activity. Twenty healthy volunteers were studied before and after 15 d of controlled white or red wine intake (300 mL/d). After wine intake, plasma resveratrol and the release of NO by stimulated platelets increased significantly. Resveratrol, at the concentrations detected in plasma after wine intake, was incubated in vitro with washed platelets and several variables related to NO production and to signal transduction were measured. Resveratrol in vitro enhanced significantly the production of NO by stimulated platelets, the activity of platelet NO synthase (NOS), phosphorylation of protein kinase B, an activator of the endothelial NOS (eNOS), and phosphorylation of vasodilator-activated protein (VASP), an expression of the biologic activity of NO in platelets. Simultaneously, we observed decreased phosphorylation of P38 mitogen-activated protein kinase (p38MAPK), a proinflammatory pathway in human platelets, a reduction of the activity of NADPH oxidase, a major source of reactive oxygen species (ROS) and of the generation of O(2)(-) radicals, as detected by cytochrome C reduction. In conclusion, resveratrol, at concentrations attainable after moderate wine intake, activates platelet eNOS and in this way blunts the proinflammatory pathway linked to p38MAPK, thus inhibiting ROS production and ultimately platelet function. This activity may contribute to the beneficial effects of moderate wine intake on ischemic cardiovascular disease.

Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure

“…Compared to placebo, our lowest dose (30mg) was shown to significantly improve FMD. A recent in vitro study (25) has shown that NO production could be enhanced in platelet cells of healthy adults after 15 days of moderate red wine consumption (300mL/day), which was associated with only a small amount of resveratrol (0.5μmol/L) in the plasma. However, other polyphenols present in the red wine may have contributed to the increased NO production.…”

“…The purported cardiovascular benefits of resveratrol from experimental evidence include defence against ischaemic-reperfusion injury (21)(22)(23), suppression of platelet aggregation (16,24), enhanced antioxidant status (16,25) and increased NO bioavailability through enhanced endothelial NO synthase expression in cultured human endothelial cells (14)(15). Recently, the progression of endothelial dysfunction and vascular remodelling in rats with pulmonary and cardiac abnormalities were slowed after three weeks of daily resveratrol administration (25mg/kg) (26).…”

Resveratrol and health – A comprehensive review of human clinical trials

“…Gresele et al [35] found 15 days of 300 mL wine consumption to increase plasma resveratrol concentration (total, including metabolites, precluding accurate conversion to mg/L) from 0.7270.3 to 1.3370.3 mmol/L for white wine (0.25 g polyphenols/L) and from 0.7170.2 to 1.7270.1 mmol/L for red wine (1.8 g polyphenols/ L). Red wine increased plasma resveratrol by 1.0 mmol/L, whereas white wine increased plasma resveratrol concentration by 0.6 mmol/L.…”

“…The activities of various resveratrol metabolites remain an open question. Reporting of plasma resveratrol measurements has been inconsistent, with researchers employing a variety of analytical chemistry techniques, and with some reporting concentrations of resveratrol and its metabolites separately [29] and others reporting combined measurements [35]. Animal models have suggested that metabolites of resveratrol may be converted back into resveratrol at the tissue level, although this has not been rigorously demonstrated [29,42].…”

Polyphenols from red wine are potent modulators of innate and adaptive immune responsiveness

“…Zn and Se) as potentiators of the immune response. increased GLUT-4 expression and reduced endothelin expression and cardiac apoptosis in a genetic model of type-2 diabetes (87) ; increased insulin sensitivity caused by a decrease of the blood glucose level in mice fed a high-energy diet (88) ; attenuation of diabetic nephropathy in rats (89) ; protection of the brain from traumatic injury (90) ; inhibition of excitatory synaptic transmission in the rat hippocampus (91,92) ; neuroprotection mediated by decreased oxidative stress and increased NO release (93) . …”