The mechanism of endothelium-independent relaxation induced by the wine polyphenol resveratrol in human internal mammary artery

Abstract

Resveratrol, a stilbene polyphenol found in grapes and red wine, produces vasorelaxation in both endothelium-dependent and endothelium-independent manners. The mechanisms by which resveratrol causes vasodilatation are uncertain. The aim of this study was to investigate the mechanism(s) of endothelium-independent resveratrol-induced vasorelaxation in human internal mammary artery (HIMA) obtained from male patients undergoing coronary artery bypass surgery and to clarify the contribution of different K+ channel subtypes in resveratrol action in this blood vessel. HIMA rings without endothelium were precontracted with phenylephrine. Resveratrol induced a concentration-dependent relaxation of the HIMA. A highly selective blocker of ATP-sensitive K+ channels, glibenclamide, as well as nonselective blockers of Ca2+-sensitive K+ channels, tetraethylammonium and charybdotoxin, did not block resveratrol-induced relaxation of HIMA rings. 4-Aminopyridine (4-AP), non selective blocker of voltage-gated K+ (Kv) channels, and margatoxin that inhibits Kv1.2, K v1.3, and Kv1.6 channels abolished relaxation of HIMA rings induced by resveratrol. In conclusion, we have shown that resveratrol potently relaxed HIMA rings with denuded endothelium. It seems that 4-AP- and margatoxin-sensitive K+ channels located in smooth muscle of HIMA mediated this relaxation. ©2006 The Japanese Pharmacological Society.