Novaković, R. (36947545500)R. (36947545500)NovakovićRadunović, N. (7003538030)N. (7003538030)RadunovićMarković-Lipkovski, J. (6603725388)J. (6603725388)Marković-LipkovskiĆirović, S. (36027425000)S. (36027425000)ĆirovićBeleslin-Čokić, B. (6506788366)B. (6506788366)Beleslin-ČokićIlić, B. (55621796900)B. (55621796900)IlićIvković, B. (23485559900)B. (23485559900)IvkovićHeinle, H. (7003342814)H. (7003342814)HeinleŽivanović, V. (6602108920)V. (6602108920)ŽivanovićGojković-Bukarica, Lj. (6602830901)Lj. (6602830901)Gojković-Bukarica2025-06-122025-06-122015https://doi.org/10.1093/molehr/gav011https://www.scopus.com/inward/record.uri?eid=2-s2.0-84942107911&doi=10.1093%2fmolehr%2fgav011&partnerID=40&md5=7d260c2a81ead6156f2244f0d6ec4061https://remedy.med.bg.ac.rs/handle/123456789/8234The 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 (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 (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, BKCa and Kv channel proteins in pregnant myometrium. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.ContractionK⁺-channelsMyometriumPregnancyResveratrol