PMID- 26189024 OWN - NLM STAT- MEDLINE DCOM- 20160721 LR - 20220311 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 764 DP - 2015 Oct 5 TI - Effect of silodosin, a selective alpha(1A)-adrenoceptor antagonist, on voiding behavior and bladder blood flow in a rat model of bladder outlet obstruction. PG - 489-496 LID - S0014-2999(15)30165-5 [pii] LID - 10.1016/j.ejphar.2015.07.037 [doi] AB - This study was performed to investigate the effects of silodosin (selective alpha1A-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 alpha1-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 alpha1-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 alpha1-adrenoceptor subtype mRNAs. The results presented here suggest that silodosin improves voiding behavior in rat models with BOO by inducing recovery of BBF. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Goi, Yoshiaki AU - Goi Y AD - Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan. Electronic address: yoshiaki_goi@pharm.kissei.co.jp. FAU - Tomiyama, Yoshitaka AU - Tomiyama Y AD - Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan. FAU - Yokoyama, Ayaka AU - Yokoyama A AD - Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan. FAU - Tatemichi, Satoshi AU - Tatemichi S AD - Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan. FAU - Maruyama, Kazuyasu AU - Maruyama K AD - Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan. FAU - Kobayashi, Mamoru AU - Kobayashi M AD - Pharmacology Research Laboratory, Kissei Pharmaceutical Co. Ltd., Azumino City, Japan. FAU - Yamaguchi, Osamu AU - Yamaguchi O AD - Division of Bioengineering and LUTD Research, Nihon University School of Engineering, Koriyama City, Japan. LA - eng PT - Journal Article DEP - 20150717 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (ADRA1A protein, human) RN - 0 (Adra1a protein, rat) RN - 0 (Adrenergic alpha-1 Receptor Antagonists) RN - 0 (Indoles) RN - 0 (Receptors, Adrenergic, alpha-1) RN - 0 (Urological Agents) RN - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine) RN - 9061-61-4 (Nerve Growth Factor) RN - CUZ39LUY82 (silodosin) RN - G9481N71RO (Deoxyguanosine) SB - IM MH - 8-Hydroxy-2'-Deoxyguanosine MH - Adrenergic alpha-1 Receptor Antagonists/*pharmacology MH - Animals MH - Blood Flow Velocity MH - Deoxyguanosine/analogs & derivatives/urine MH - Disease Models, Animal MH - Female MH - Immunohistochemistry MH - In Situ Hybridization MH - Indoles/*pharmacology MH - Laser-Doppler Flowmetry MH - Microcirculation/*drug effects MH - Nerve Growth Factor/urine MH - Rats, Sprague-Dawley MH - Receptors, Adrenergic, alpha-1/*drug effects/genetics/metabolism MH - Regional Blood Flow MH - Time Factors MH - Ureteral Obstruction/complications MH - Urinary Bladder/blood supply/*drug effects/innervation/metabolism MH - Urinary Bladder Neck Obstruction/*drug therapy/etiology/genetics/metabolism/physiopathology MH - Urination/*drug effects MH - Urodynamics/*drug effects MH - Urological Agents/*pharmacology OTO - NOTNLM OT - Bladder blood flow OT - Bladder outlet obstruction OT - Ischemia OT - Nerve growth factor OT - Silodosin OT - Silodosin (PubChem CID: 5312125) OT - alpha(1A)-Adrenoceptor EDAT- 2015/07/21 06:00 MHDA- 2016/07/22 06:00 CRDT- 2015/07/20 06:00 PHST- 2015/03/24 00:00 [received] PHST- 2015/06/18 00:00 [revised] PHST- 2015/07/15 00:00 [accepted] PHST- 2015/07/20 06:00 [entrez] PHST- 2015/07/21 06:00 [pubmed] PHST- 2016/07/22 06:00 [medline] AID - S0014-2999(15)30165-5 [pii] AID - 10.1016/j.ejphar.2015.07.037 [doi] PST - ppublish SO - Eur J Pharmacol. 2015 Oct 5;764:489-496. doi: 10.1016/j.ejphar.2015.07.037. Epub 2015 Jul 17.