title: Silodosin, an α(1A)-Adrenoceptor Antagonist, May Ameliorate Ischemia-Induced Bladder Denervation and Detrusor Dysfunction by Improving Bladder Blood Flow.
abstract: OBJECTIVE
  This study was performed to investigate the detailed mechanism underlying the effects of the selective α(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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Goi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: Itaru
authors.initials: I
authors.lastname: Maruyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tatemichi
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Maruyama
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomiya
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology*; D007511:Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000098:blood supply / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000235:genetics / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000235:genetics / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D001743:Urinary Bladder / Q000098:blood supply / Q000294:innervation / Q000473:pathology / Q000503:physiopathology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D020932:Nerve Growth Factor; C095285:silodosin; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase