The wine polyphenol resveratrol relaxes smooth muscles of the non-pregnant rat uterus

RB Novakovic1, DD Protic1, NV Radunovic2, HH Heinle3, VI Kanjuh4, LC Gojkovic-Bukarica1. 1University of Belgrade, Medical faculty, Institute of Pharmacology, Clinical Pharmacology and Toxicology, Serbia, 2University of Belgrade, Clinical Center of Serbia, Institute of Gynecology and Obstetrics, Serbia, 3University of Tuebingen, Institute of Physiology, Germany, 4Academy of Sciences and Arts, Department of Medical Sciences, Serbia

Resveratrol (RSV) is a phytoalexin produced by grapevines. The benefit of resveratrol to health is widely reported. Resveratrol has been found to promote vascular relaxation but its mechanism of action is unclear. The data about influence of RSV on the contractility of smooth muscles of uterus are not available. The aims of our study were to investigate the effects of RSV on the contractility of rat uterus and to investigate the involvement of K+ channels in effect of RSV on the spontaneous contractions (SC) and contractions provoked by oxytocin.

Uterine strips were obtained from virgin female Wistar rats in oestrus. Strips were mounted into organ bath for recording isometric tension in Krebs-Ringer solution aerated with 95% O2 and 5% CO2 at 37 °C. RSV (1 – 100 μM) was added to the bath cumulatively. In order to test the involvement of K+ channels in the mechanism of action of RSV, a selective blocker of KATP channels, glibenclamide (GLB), a non-selective blocker of Kir chnannel, BaCl2 (1 mM), a non-selective blocker of Kv channels, 4-aminopiridine (4-AP) and tetraethylamonium (TEA), a non-selective blocker of BKCa channels were tested. Experiments followed a multiple curve design. The results are expressed as the means ± standard error of the mean (S.E.M.). Statistical difference between means was determined by Student’s t-test, a value of P < 0.05 was considered statistically significant.

RSV induced a concentration-dependent relaxation of SC (pD2=4.53 and Emax=94%) and contractions provoked by oxytocin (pD2=4.66 and Emax=95%, P<0.05). GLB (10 µM), 4-AP (1 mM), TEA (1 mM), BaCl2 (1 mM) antagonized the response to RSV in both, oxytocin induced contractions (with pD2 values 4.26, 4.19, 4.34, 4.02, n=6-9) and SC (with pD2 values 4.30, 4.40, 4.38, 4.20, n=6-9). Relaxation achieved by concentration of 100 µM RSV was insensitive to K+ channel blockers.

RSV is uterine relaxant and can be use in tocolysis. The antagonism of RSV effect by a different K+ channels blockers suggests that K+-channels are involved in resveratrol action on the contractions of rat uterus. It seems that RSV, when applied in high concentration, may exert an additional mechanism of action.