Effect of naftopidil, an alpha1D/A-adrenoceptor antagonist, on the urinary bladder in rats with spinal cord injury

Aims: Alphanyadrenoceptors (alpha(1D)-ARs) located in the spinal cord are involved in the control of lower urinary tract function. In order to clarify the effect of alpha(1D)-ARs on storage function in the spinal cord, we examined the effect of oral administration and intrathecal injection of the alpha(1D/A)-AR antagonist, naftopidil, on bladder activity, as well as the effect of naftopidil on bladder wall histology, in female rats with spinal cord injury (SCI). Main methods: Adult female Sprague-Dawley rats with Th9-10 spinal cord transection were used. In SCI rats with or without 5 mg/day of naftopidil for 4 weeks, bladder activity was examined via continuous cystometry. In other SCI rats, bladder activity was examined before and after intrathecal injection of naftopidil. In addition, bladder wall histology was compared between SCI rats with or without oral administration of naftopidil for 4 weeks. Key findings: Oral administration of naftopidil decreased the number of non-voiding contractions (NVCs). Intrathecal injection of naftopidil prolonged the interval between voiding contractions, decreased the maximum voiding contraction pressure and the number of NVCs, and increased bladder capacity without affecting the residual urine volume. Oral administration of naftopidil also decreased bladder wall fibrosis. Significance: The alpha(1D/A)-AR antagonist naftopidil might act on the bladder and spinal cord to improve detrusor hyperreflexia in the storage state in SCI female rats. Naftopidil also suppressed bladder wall fibrosis, suggesting that it may be effective for the treatment of neurogenic lower urinary tract dysfunction after SCI. (C) 2013 Elsevier Inc. All rights reserved.