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.
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-RTXrats, but unchanged in RTXrats. Silodosin (i.a.) significantly prolonged BCI in non-RTXrats 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.
Authors: K Akiyama; M Hora; S Tatemichi; N Masuda; S Nakamura; R Yamagishi; M Kitazawa Journal: J Pharmacol Exp Ther Date: 1999-10 Impact factor: 4.030
Authors: Christian Hampel; Paul C Dolber; Michael P Smith; Sandra L Savic; Joachim W Th roff; Karl B Thor; Debra A Schwinn Journal: J Urol Date: 2002-03 Impact factor: 7.450
Authors: B J Malloy; D T Price; R R Price; A M Bienstock; M K Dole; B L Funk; X L Rudner; C D Richardson; C F Donatucci; D A Schwinn Journal: J Urol Date: 1998-09 Impact factor: 7.450
Authors: Christopher L Langdale; James A Hokanson; Philip H Milliken; Arun Sridhar; Warren M Grill Journal: Am J Physiol Renal Physiol Date: 2020-04-20