Resveratrol attenuates angiotensin II-induced interleukin-6 expression and perivascular fibrosis

Recent studies have shown that resveratrol (3,5,4′-trihydroxystilbene), a polyphenolic compound found in grapes and red wine, has various beneficial effects on cardiovascular diseases and prolongs the life span of mice fed a high-fat diet. We hypothesized that resveratrol may attenuate vascular inflammatory response induced by angiotensin (Ang) II. We examined the effect of resveratrol on Ang II-induced interleukin (IL)-6 expression in vascular smooth muscle cells (VSMCs). Resveratrol significantly attenuated Ang II-induced IL-6 mRNA expression and IL-6 protein in the supernatant of VSMC in a dose-dependent manner. Resveratrol suppressed the IL-6 gene promoter activity. Resveratrol inhibited the Ang II-induced cAMP-response element-binding protein and nuclear factor-kappa B activity, which are critical for Ang II-induced IL-6 gene activation. An increase in the serum concentration of IL-6 induced by Ang II infusion was attenuated by an oral administration of resveratrol. Resveratrol also inhibited Ang II-induced hypertension and perivascular fibrosis of the heart. Although hydralazine reduced blood pressure level equal to resveratrol, it did not reduce the Ang II-induced IL-6 production and perivascular fibrosis. These data suggest that the inhibition of Ang II-induced vascular inflammation and high blood pressure by resveratrol may contribute, at least in part, to the anti-atherogenic effects of resveratrol.