Resveratrol recruits rat muscle microvasculature via a nitric oxide-dependentmechanism that is blocked by TNFalpha.

摘要

Resveratrol, a polyphenol found in many plants, has antioxidant andanti-inflammatory actions. It also improves endothelial function and may becardioprotective. Tumor necrosis factor-alpha (TNFalpha) causes oxidative stress andmicrovascular endothelial dysfunction. Whether resveratrol affects microvascular function in vivo and, if so, whether inflammatory cytokines antagonize itsmicrovascular action are not clear. In cultured bovine aortic endothelial cells(BAECs), resveratrol (100 nM) increased the phosphorylation of protein kinase B(Akt), endothelial nitric oxide (NO) synthase (eNOS), and ERK1/2 within 15 min bymore than twofold, and this effect lasted for at least 2 h. Treatment of BAECswith TNFalpha (10 ng/ml) significantly increased the NADPH oxidase activity and theproduction of hydrogen peroxide and superoxide. Pretreatment of cells withresveratrol (100 nM) prevented each of these. Injection (ip) of resveratrol inrats potently increased muscle microvascular blood volume (MBV; P = 0.007) andflow (MBF; P < 0.02) within 30 min, and this was sustained for at least 2 h. The phosphorylation of Akt in liver or muscle was unchanged. Superimposed systemicinfusion of L-NAME (NOS inhibitor) completely abolished resveratrol-inducedincreases in MBV and MBF. Similarly, systemic infusion of TNFalpha preventedresveratrol-induced muscle microvascular recruitment. In conclusion, resveratrol activates eNOS and increases muscle microvascular recruitment via an NO-dependentmechanism. Despite the potent antioxidant effect of resveratrol, TNFalpha atconcentrations that block insulin-mediated muscle microvascular recruitmentcompletely neutralized resveratrol's microvascular action. Thus, chronicinflammation, as seen in type 2 diabetes, may limit resveratrol's vasodilatoryactions on muscle microvasculature.