Regulation of Spontaneous Contractions in Intact Rat Bladder Strips and the Effects of Hydrogen Peroxide.

Mingshuai Wang,Wen-Chu Huang,Guiming Liu,Liyang Wu,Nianzeng Xing,Zhenqun Xu

doi:10.1155/2018/2925985

Abstract

Enhanced spontaneous contractions are associated with overactive bladder. Elevated levels of reactive oxygen species might contribute to enhanced spontaneous contractions. We investigated the regulation of spontaneous contractions and the effects of hydrogen peroxide (H2O2) in intact rat bladder strips. The spontaneous contractions were measured using a tissue bath system. The vehicle or the specific activators/blockers were applied and followed by the application of 0.003 g% H2O2. The basal tension, amplitude, and frequency of spontaneous contractions were quantified. Nisoldipine and bisindolylmaleimide 1 had no effects on spontaneous contractions. SKF96365 and Y27632 decreased basal tension and amplitude. Ryanodine slightly increased frequency. Both iberiotoxin and NS-1619 increased amplitude. Apamin reduced frequency but increased amplitude. NS-309 inhibited both the amplitude and frequency. The basal tension and amplitude increased when H2O2 was applied. Pretreatment with NS-309 inhibited H2O2-elicited augmented amplitude and frequency, while pretreatment with Y-27632 inhibited the augmented basal tension. The combined application of NS-309 and Y27632 almost eliminated spontaneous contractions and its augmentation induced by H2O2. In conclusion, Ca2+ influx, Rho kinase activation, and SK channel inactivation play important roles in spontaneous contractions in intact bladder strips, whereas only latter two mechanisms may be involved in H2O2-elicited increased spontaneous contractions.

Highlights

The urinary bladder has two important functions, which are to store and expel urine
Nisoldipine had no significant effect on spontaneous contractions of intact bladder strips (Figure 1, Table 1), whereas SKF96365 decreased the amplitude dramatically and basal tension slightly (Figure 1, Table 1)
The results showed that combined application of Y27632 and NS-309 significantly prevented the H2O2-induced increases of basal tension, amplitude, and frequency of the spontaneous contractions

Summary

Introduction

The detrusor smooth muscle of the bladder exhibits spontaneous contractile activity during the filling phase and in isolated detrusor strips [1, 2]. The spontaneous activity cannot be abolished by tetrodotoxin, atropine, phentolamine, propranolol, or hexamethonium, indicating that the activity is not dependent on innervation [1, 2]. The role of spontaneous activity may be to facilitate adjustment of muscle bundle lengths during bladder filling [3, 4]. Previous studies using denuded detrusor muscle strips suggested that calcium channels [7], largeconductance calcium-activated potassium [BK] channel [8], small-conductance calcium-activated potassium [SK] channel [9], Rho-associated coiled-coil kinase (ROCK) [10], and protein kinase C (PKC) [11] contributed to the regulation of smooth muscle spontaneous contractions

Methods

Results

Discussion

Conclusion