Silodosin, an alpha(1A)-Adrenoceptor Antagonist, May Ameliorate Ischemia-Induced Bladder Denervation and Detrusor Dysfunction by Improving Bladder Blood Flow

摘要

Background/Aims: This study was performed to investigate the detailed mechanism underlying the effects of the selective alpha(1A)-adrenoceptor antagonist, silodosin, on bladder function in a rat model of atherosclerosis-induced chronic bladder ischemia (CBI). Methods: The CBI model was prepared by balloon endothelial injury of the bilateral iliac arteries in male rats. Using an osmotic pump, the CBI rats received either silodosin or vehicle alone subcutaneously for 8 weeks. Rats received a 2% cholesterol diet throughout the experiment. Bladder blood flow (BBF) was measured. Immunohistochemical staining was performed to determine the nerve distribution and nerve growth factor expression in the bladder. Bladders were used for muscle strip contraction analysis. The expression levels of muscarinic M2 and M3 receptors were measured. Results: Silodosin abrogated the decrease in BBF in CBI rats. Silodosin prevented the decrease in nerve distribution and increase in nerve growth factor expression in the CBI model. Bladder contractile response was reduced in the CBI group. Silodosin ameliorated the effect on the bladder contractile response. The level of muscarinic M3 receptor mRNA present in the bladder of CBI rats was increased by silodosin. Conclusion: The results of this study suggest that silodosin ameliorates the denervation of the bladder and effects on detrusor contractile function under ischemic conditions by restoring BBF. (C) 2016 S. Karger AG, Basel