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.
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Keita
K
Inanaga
Toshihiro
T
Ichiki
Hirohide
H
Matsuura
Ryohei
R
Miyazaki
Toru
T
Hashimoto
Kotaro
K
Takeda
Kenji
K
Sunagawa
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis; D006339:Heart Rate / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014652:Vascular Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D000975:Antioxidants; D015850:Interleukin-6; D013267:Stilbenes; D000804:Angiotensin II; D004247:DNA; D008156:Luciferases; D000077185:Resveratrol