Effect of low concentrations of hydrogen peroxide on the contractile responses of rat detrusor smooth muscle strips

Abstract

This study was designed to determine how the contractility of rat detrusor smooth muscle strips changes in the presence of low concentrations of hydrogen peroxide (H2O2). The strips were dissected from the base of Sprague-Dawley rat bladders and their contractile responses to a cumulative increase in H2O2 concentration (3 x 10(-6) - 3 x 10(-2) g%) were measured. How the duration of exposure to the fixed concentration of 3 x 10(-4) g% H2O2 affected contractility was also examined. Moreover, the effect of 3 x 10(-4) g% H2O2 pretreatment on the response to cumulative increases in the concentrations of phenylephrine or acetylcholine (10(-8)-10(-4) M) was assessed. To elucidate the mechanism by which H2O2 induced contraction, we examined the effect of pretreatment with 10 nMY-27632, 10 mu M indomethacin, 10 mu M SQ29548, 10 mu M verapamil, 10 mu M vitamin E, or 1 mu M Bay-K8644 on the contractile responses generated by cumulatively increasing the concentration of H2O2. H2O2-induced contractile responses in Ca2+-free physiological solution were also examined. Low concentrations of H2O2 increased the contractile responses of the strips in a dose-dependent manner but increasing treatment duration decreased these responses. H2O2-pretreatment significantly augmented the contraction induced by phenylephrine (P<0.05) but had no effect on the response to acetylcholine. Pretreatment with Y-27632, indomethacin, vitamin E, verapamil, and Bay-K 8644 significantly inhibited the H2O2-induced contraction (P<0.05). SQ 29548-pretreatment had no effect. H2O2 could not increase the contractile responses in Ca2+-free physiological solution. Thus, low concentrations of H2O2 may directly affect detrusor smooth muscles and thereby induce detrusor overactivity. (C) 2010 Elsevier B.V. All rights reserved.