title: Effect of silodosin, a selective α(1A)-adrenoceptor antagonist, on voiding behavior and bladder blood flow in a rat model of bladder outlet obstruction.
abstract: This study was performed to investigate the effects of silodosin (selective α1A-adrenoceptor antagonist) on bladder blood flow (BBF) and bladder function in a rat model of bladder outlet obstruction (BOO) and to determine the expression of α1-adrenoceptor subtype mRNA in human and rat bladder microvessels. BOO was produced by partial ligature of the proximal urethra, which was maintained for 2 weeks. The BOO rats received either silodosin at a rate of 0.3mg/kg/day or vehicle subcutaneously via an osmotic pump for 2 weeks after BOO surgery. A metabolic cage study was performed in conscious animals. BBF was measured using a Laser Speckle Blood Flow Imager. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nerve growth factor (NGF) were measured. Immunohistological examinations of nerve distribution and NGF expression in the rat bladder were conducted. The expression of each α1-adrenoceptor subtype mRNA in human and rat bladder microvessels was determined by in situ hybridization. Silodosin ameliorated the increase in voiding frequency and decrease in mean voided volume in BOO rats in the metabolic cage study. Silodosin also abrogated the decrease in BBF in BOO rats. The levels of 8-OHdG and NGF in BOO rats were significantly decreased by administration of silodosin. Silodosin prevented the decrease in nerve distribution and increase in NGF expression. Human and rat bladder microvessels showed expression of all α1-adrenoceptor subtype mRNAs. The results presented here suggest that silodosin improves voiding behavior in rat models with BOO by inducing recovery of BBF.
authors.affiliation: Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan. Electronic address: yoshiaki_goi@pharm.kissei.co.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Goi
authors.affiliation: Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tomiyama
authors.affiliation: Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Yokoyama
authors.affiliation: Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tatemichi
authors.affiliation: Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan.
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Maruyama
authors.affiliation: Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Division of Bioengineering and LUTD Research, Nihon University School of Engineering, Koriyama City, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007211:Indoles / Q000494:pharmacology*; D017078:Laser-Doppler Flowmetry; D008833:Microcirculation / Q000187:drug effects*; D020932:Nerve Growth Factor / Q000652:urine; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012039:Regional Blood Flow; D013997:Time Factors; D014517:Ureteral Obstruction / Q000150:complications; D001743:Urinary Bladder / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D014554:Urination / Q000187:drug effects*; D014563:Urodynamics / Q000187:drug effects*; D064804:Urological Agents / Q000494:pharmacology*
chemical_list: C547713:ADRA1A protein, human; C547715:Adra1a protein, rat; D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D018340:Receptors, Adrenergic, alpha-1; D064804:Urological Agents; D000080242:8-Hydroxy-2'-Deoxyguanosine; D020932:Nerve Growth Factor; C095285:silodosin; D003849:Deoxyguanosine
keywords: Bladder blood flow; Bladder outlet obstruction; Ischemia; Nerve growth factor; Silodosin; Silodosin (PubChem CID: 5312125); α(1A)-Adrenoceptor