| 19917063 |
Appiah I, Milovanovic S, Radojicic R, Nikolic-Kokic A, Orescanin-Dusic Z, Slavic M, Trbojevic S, Skrbic R, Spasic MB, Blagojevic D: Hydrogen peroxide affects contractile activity and anti-oxidant enzymes in rat uterus. Br J Pharmacol. 2009 Dec;158(8):1932-41. Epub .
BACKGROUND AND PURPOSE: The effects of hydrogen peroxide (H (2) O (2)) 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 (Ca (2+))-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 Ca (2+) (6 mM) and treated with H (2) O (2) (2 microM-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 H (2) O (2)-treated uteri were compared with those in uteri immediately frozen after isolation or undergoing spontaneous or Ca (2+)-induced contractions, without treatment with H (2) O (2). The effect of inhibitors (propranolol, methylene blue, L-NAME, tetraethylamonium, glibenclamide and 4-aminopyridine) on H (2) O (2)-mediated relaxation was explored. KEY RESULTS: H (2) O (2) caused concentration-dependent relaxation of both spontaneous and Ca (2+)-induced uterine contractions. After H (2) O (2) treatment, GSHPx and MnSOD activities were increased, while CuZnSOD and GR (In Ca (2+)-induced rat uteri) were decreased. N (omega)-nitro-L-arginine methyl ester antagonized the effect of H (2) O (2) on Ca (2+)-induced contractions. H (2) O (2)-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: H (2) O (2) 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. |
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