Heme oxygenase-1 contributes to the protective effect of resveratrol against endothelial dysfunction in STZ-induced diabetes in rats.

Endothelial dysfunction is a common complication of diabetes that mainly stems from increased reactive oxygen species, which makes antioxidants of great benefit. Resveratrol (RSV) is an antioxidant that shows protective effects in a variety of disease models where the ameliorative effect appears to be mediated, in part, via heme oxygenase-1 (HO-1) induction. However, the pathophysiological relevance of HO-1 in the ameliorative response of RSV in endothelial dysfunction is not clearly defined. The present study was conducted to investigate whether HO-1 plays a role in diabetes-induced vascular dysfunction. Streptozotocin-diabetic rats were treated with RSV (10 mg/kg) in presence or absence of an HO-1 blocker, Zinc protoporphyrin (ZnPP) to assess vascular function and indicators of disease status. We found that RSV treatment significantly abrogated diabetes induced vascular dysfunction. This improvement was associated with the ability of RSV to decrease oxidative stress markers alongside a reduction in the aortic TGF-β expression, elevation of NOS3 expression and aortic nitrite concentration as well as HO activity. These ameliorative effects were diminished when ZnPP was administered prior to RSV. Our results clearly demonstrate the protective effects of RSV in diabetes-associated endothelial dysfunction and verified a causal role of HO-1 in this setting.