title: Effects of silodosin, a selective α1A-adrenoceptor antagonist, on bladder blood flow and bladder function in a rat model of atherosclerosis induced chronic bladder ischemia without bladder outlet obstruction.
abstract: OBJECTIVE
  We investigated the effects of the selective α1A-adrenoceptor antagonist silodosin on bladder blood flow and bladder function in a rat model of atherosclerosis induced chronic bladder ischemia without bladder outlet obstruction.
  
  
  METHODS
  The chronic bladder ischemia model was prepared by creating balloon endothelial injury of the bilateral iliac arteries in male rats. Using an osmotic pump, chronic bladder ischemia rats received silodosin subcutaneously at a rate of 0.1 or 0.3 mg/kg per day, or vehicle for 8 weeks. All groups received a 2% cholesterol diet throughout the experiment. For each α1-adrenoceptor subtype mRNA expression in bladder microvessels was examined by in situ hybridization. Bladder blood flow was measured using a laser speckle blood flow imager. Malondialdehyde in bladder tissue and 8-hydroxy-2'-deoxyguanosine in urine were measured as markers of oxidative stress. A metabolic cage study and cystometry were performed in conscious rats.
  
  
  RESULTS
  The expression of all α1-adrenoceptor subtype mRNA was observed in rat bladder microvessels. Silodosin abrogated the decreased bladder blood flow in the empty bladder and during bladder distention that were evident in rats with chronic bladder ischemia. Levels of oxidative stress markers in these rats were significantly decreased by silodosin administration. Silodosin ameliorated bladder dysfunction in rats with chronic bladder ischemia in the metabolic cage study and on cystometry.
  
  
  CONCLUSIONS
  Results suggest that in ischemic conditions α1-adrenoceptor antagonists such as silodosin may improve bladder function by restoring bladder blood flow.
authors.affiliation: Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan. yoshiaki_goi@pharm.kissei.co.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Goi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomiya
authors.forename: Koji
authors.initials: K
authors.lastname: Sagawa
authors.forename: Ken
authors.initials: K
authors.lastname: Aikawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007211:Indoles / Q000494:pharmacology*; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000098:blood supply* / Q000187:drug effects*; D001748:Urinary Bladder Neck Obstruction
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; C095285:silodosin
keywords: 8-OHdG; 8-hydroxy-2′-deoxyguanosine; AR; BBF; BOO; BPH; CBI; DO; I/R; KMD 3213; LUTS; MDA; ROS; adrenergic alpha-1 receptor antagonists; adrenoceptor; atherosclerosis; benign prostatic hyperplasia; bladder blood flow; bladder outlet obstruction; chronic bladder ischemia; detrusor overactivity; ischemia; ischemia and reperfusion; lower urinary tract symptoms; malondialdehyde; reactive oxygen species; urinary bladder