Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium

Abstract

The ideal agent for prevention and treatment of uterine abnormal contractility has not been found. The polyphenol resveratrol possesses a wide spectrum of pharmacologic properties, but its influence on the contractility of human myometrium is not defined. The present study evaluated the effect of resveratrol on the oxytocin-induced contractions of human term pregnant myometrium in vitro and the contribution of different K+ channels to resveratrol action. Resveratrol induced a concentration-dependent relaxation of myometrium contractions (pD(2) value and maximal responses were 4.52 and 82.25%, respectively). Glibenclamide, a selective blocker of ATP-sensitive (K-ATP), iberiotoxin, a selective blockers of big-calcium sensitive (BKCa) and 4-aminopiridine, a non-selective blocker of voltage-sensitive (Kv) channels induced a significant shift to the right of the concentration-response curves of resveratrol. Inhibition achieved by 0.1 mM resveratrol was insensitive to all K+ channel blockers. A K+ channel opener, pinacidil, inhibited oxytocin-induced contractions of pregnant myometrium with comparable potency and efficacy to resveratrol (pD(2) values and maximal relaxation were 4.52 and 83.67%, respectively). Based on K+ channel opener/blocker affinities, it appears that the inhibitory response of resveratrol involves different myometrial K+ channels. When applied in high concentrations, resveratrol has an additional K+-channel-independent mechanism(s) of action. Furthermore, immunohistochemistry staining and western blot analyses detected the presence and distribution of K-ATP, BKCa and Kv channel proteins in pregnant myometrium.