Hydrogen peroxide affects contractile activity and anti-oxidant enzymes in rat uterus

Background and purpose: The effects of hydrogen peroxide (H2O2) on uterine smooth muscle are not well studied. We have investigated the effect and the mechanism of action of exogenous hydrogen peroxide on rat uteri contractile activity [spontaneous and calcium ion (Ca2+)-induced] and the effect of such treatment on anti-oxidative enzyme activities. Experimental approach: Uteri were isolated from virgin Wistar rats and suspended in an organ bath. Uteri were allowed to contract spontaneously or in the presence of Ca2+ (6 mM) and treated with H2O2 (2 mu M-3 mM) over 2 h. Anti-oxidative enzyme activities (manganese superoxide dismutase-MnSOD, copper-zinc superoxide dismutase-CuZnSOD, catalase-CAT, glutathione peroxidase-GSHPx and glutathione reductase-GR) in H2O2-treated uteri were compared with those in uteri immediately frozen after isolation or undergoing spontaneous or Ca2+-induced contractions, without treatment with H2O2. The effect of inhibitors (propranolol, methylene blue, L-NAME, tetraethylamonium, glibenclamide and 4-aminopyridine) on H2O2-mediated relaxation was explored. Key results: H2O2 caused concentration-dependent relaxation of both spontaneous and Ca2+-induced uterine contractions. After H2O2 treatment, GSHPx and MnSOD activities were increased, while CuZnSOD and GR (In Ca2+-induced rat uteri) were decreased. N omega-nitro-L-arginine methyl ester antagonized the effect of H2O2 on Ca2+-induced contractions. H2O2-induced relaxation was not affected by propranolol, potentiated by methylene blue and antagonized by tetraethylamonium, 4-aminopyridine and glibenclamide, with the last compound being the least effective. Conclusions and implications: H2O2 induced dose-dependent relaxation of isolated rat uteri mainly via changes in voltage-dependent potassium channels. Decreasing generation of reactive oxygen species by stimulation of anti-oxidative pathways may lead to new approaches to the management of dysfunctional uteri.