Selective α1A-blocker improves bladder storage function in rats via suppression of C-fiber afferent activity

Purpose In the present study, we used animal models to investigate whether the selective α 1A -blocker silodosin exerts inhibitory effects on detrusor overactivity by modulating C-fiber afferent activity. Methods To desensitize C-fiber afferents, 0.3 mg/kg of resiniferatoxin (RTX) was subcutaneously injected into some female Sprague–Dawley rats 2 days before creation of each model. (1) Left middle cerebral artery occlusion was performed to create a cerebral infarction (CI) model (CI rats). The effects of intravenous (i.v.) and intrathecal (i.t.) administrations of silodosin on cystometrography parameters were evaluated in conscious rats. (2) Rhythmic bladder pressure was recorded in rats under urethane anesthesia. Prostaglandin (PG) E 2 (0.4 mg/mL) was continuously administered intraurethrally, and the effects of intra-arterial (i.a.) silodosin on the micturition reflex (MR) were investigated. Results (1) Silodosin (i.v.) dose-dependently increased bladder capacity (BC) in CI rats without decreasing bladder contraction pressure, but had no effects on BC in RTX-CI rats. Silodosin (i.t.) markedly increased BC in CI rats, but not in RTX-CI rats. (2) After intraurethral administration of PGE 2 , the bladder contraction interval (BCI) was markedly reduced in non-RTX rats, but unchanged in RTX rats. Silodosin (i.a.) significantly prolonged BCI in non-RTX rats receiving intraurethral PGE 2 . Conclusions These results suggest that the α 1A -AR subtype activates C-fiber afferents, and that consequently α 1A -blockade can improve bladder storage function.