Distribution of interstitial cells of cajal and expression of nitric oxide synthase after experimental bladder outlet obstruction in a rat model of bladder overactivity

Abstract

Recent studies have showed that interstitial cells (ICs) are widely distributed in the genitourinary tract and have suggested their involvement in spontaneous electrical activity and muscle contraction. Nitric oxide (NO) is thought to play a role in bladder overactivity related with bladder outlet obstruction (BOO). The purposes of this study were to investigate the effect of bladder overactivity induced by BOO on ICs and nitric oxide synthase (NOS) isoforms in rat urinary bladder. Female Sprague-Dawley rats (230-240 g, n = 40) were divided into two groups: control (group Con, n = 20) and partial BOO (group BOO, n = 20). After 4 weeks, urodynamic studies measuring contraction interval and contraction pressure were done. The cellular localization of cKit immunoreactive ICs and the expression of endothelial NOS (eNOS) and neuronal NOS (nNOS) were determined by Western blot and immunohistochemistry in the rat urinary bladder. Filling cystometry studies demonstrated a reduced interval between voiding contractions and an increased voiding pressure in BOO bladders. The contraction interval time (2.9 ± 0.35 min) was significantly decreased in the BOO group compared to the control (6.1 ± 0.05; P < 0.05). The population of ICs was increased in the suburothelial and muscle layers in BOO bladders. ICs had a close contact with each other and neighboring nNOS expressing cells. These results demonstrated an increased population of ICs in the BOO rat model and suggest that the functional change of ICs and NOS isoforms may contribute to the pathophysiology of bladder overactivity induced by BOO.