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 (H(2)O(2)). The strips were dissected from the base of Sprague-Dawley rat bladders and their contractile responses to a cumulative increase in H(2)O(2) 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% H(2)O(2) affected contractility was also examined. Moreover, the effect of 3 x 10(-4)g% H(2)O(2) 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 H(2)O(2) induced contraction, we examined the effect of pretreatment with 10nM Y-27632, 10 microM indomethacin, 10 microM SQ29548, 10 microM verapamil, 10 microM vitamin E, or 1 microM Bay-K 8644 on the contractile responses generated by cumulatively increasing the concentration of H(2)O(2). H(2)O(2)-induced contractile responses in Ca(2+)-free physiological solution were also examined. Low concentrations of H(2)O(2) increased the contractile responses of the strips in a dose-dependent manner but increasing treatment duration decreased these responses. H(2)O(2)-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 H(2)O(2)-induced contraction (P<0.05). SQ 29548-pretreatment had no effect. H(2)O(2) could not increase the contractile responses in Ca(2+)-free physiological solution. Thus, low concentrations of H(2)O(2) may directly affect detrusor smooth muscles and thereby induce detrusor overactivity.