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

Mar 10, 2015Molecular human reproduction

Resveratrol’s effects on muscle contractions in human late-pregnancy uterus

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Abstract

Resveratrol induced a maximum relaxation of myometrium contractions of 82.25% in vitro.

Resveratrol's effect on myometrium contractions is concentration-dependent, with a pD2 value of 4.52.
Different potassium channel blockers shifted the concentration-response curves of resveratrol to the right, indicating their involvement in its action.
Inhibition by 0.1 mM resveratrol was not affected by any potassium channel blockers, suggesting a distinct mechanism.
A potassium channel opener, pinacidil, demonstrated similar potency and efficacy to resveratrol in inhibiting oxytocin-induced contractions.
Presence and distribution of KATP, BK(Ca), and Kv channel proteins were confirmed in pregnant myometrium through immunohistochemistry and western blot analyses.

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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 (pD2 value and maximal responses were 4.52 and 82.25%, respectively). Glibenclamide, a selective blocker of ATP-sensitive (KATP), iberiotoxin, a selective blockers of big-calcium sensitive (BK(Ca)) 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 (pD2 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 KATP, BK(Ca) and Kv channel proteins in pregnant myometrium.

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

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