Effect of silodosin, a selective α1A-adrenoceptor antagonist, on voiding behavior and bladder blood flow in a rat model of bladder outlet obstruction

被引：12

作者：

Goi, Yoshiaki ^{[1
]}

Tomiyama, Yoshitaka ^{[1
]}

Yokoyama, Ayaka ^{[1
]}

Tatemichi, Satoshi ^{[1
]}

Maruyama, Kazuyasu ^{[1
]}

Kobayashi, Mamoru ^{[1
]}

Yamaguchi, Osamu ^{[2
,3
]}

机构：

[1] Kissei Pharmaceut Co Ltd, Pharmacol Res Lab, Azumino City, Japan

[2] Nihon Univ, Sch Engn, Div Bioengn, Koriyama, Fukushima, Japan

[3] Nihon Univ, Sch Engn, LUTD Res, Koriyama, Fukushima, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2015年 / 764卷

关键词：

silodosin; alpha(1A)-Adrenoceptor; Bladder blood flow; Bladder outlet obstruction; Ischemia; Nerve growth factor; LOWER URINARY-TRACT; ADRENOCEPTOR SUBTYPES; CHRONIC ISCHEMIA; SYMPTOMS; EXPRESSION; ASSOCIATION; DYSFUNCTION; NAFTOPIDIL; ALPHA(1); THERAPY;

D O I：

10.1016/j.ejphar.2015.07.037

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

This study was performed to investigate the effects of silodosin (selective alpha(1A)-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 alpha(1)-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 0.3 mg/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 alpha(1)-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 alpha(1)-adrenoceptor subtype mRNAs. The results presented here suggest that silodosin improves voiding behavior in rat models with BOO by inducing recovery of BBF. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：489 / 496

页数：8

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