Resveratrol Protects Endothelial Cells from Rapid Stretch Injury and Hypoxia In Vitro

An important function of endothelial cells is to maintain a balance between the production of vasodilators such as nitric oxide (NO) and vasoconstrictors such as endothelin-1, thereby maintaining vascular tone and blood flow. However in many disease states, including hypoxia and traumatic brain injury, impaired production of NO leads to vasoconstriction, platelet aggregation and oxidative stress. Resveratrol (trans-3,4’,5-trihydroxystilbene) is a polyphenolic compound found in peanuts, mulberries and red wine. It has been shown to display antioxidant activity, inhibit platelet aggregation and induce NO production. The purpose of the present study was to determine the effect of resveratrol on cultured brain endothelial cells in two models of pathology characterized by disrupted NO production – hypoxia alone and then a combination regimen of rapid stretch injury followed by hypoxia. Mouse brain endothelial cells cultured in resveratrol caused a dose-dependent increase in endothelial nitric oxide synthase (eNOS) protein expression. Importantly, resveratrol prevented hypoxia-induced decrease in eNOS expression. This was complemented by reduced cell death, as evidenced by a reduction in propidium iodide staining. However coincubation of resveratrol with the NO inhibitor, L-NAME, did not prevent this protection. Rapid stretch injury and hypoxia produced marked cell necrosis and resveratrol significantly inhibited this death. Our results suggest that resveratrol can prevent hypoxia-induced blunting of eNOS expression and protects endothelial cells from hypoxia alone and a combined regimen of rapid stretch injury and hypoxia.