Abstract
Background: 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, impaired production of NO leads to vasoconstriction, platelet aggregation and oxidative stress. Resveratrol, a polyphenolic compound found in peanuts and red wine, has been shown to induce NO production.
Objective: 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.
Method: 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.
Results: 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.
Conclusion: This study has shown for the first time that resveratrol prevents hypoxia-induced decrease in eNOS expression and protects endothelial cells from hypoxia alone and a combined regimen of rapid stretch injury and hypoxia.
Keywords: Endothelium, nitric oxide, resveratol.
Graphical Abstract
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