Effect of silodosin on detrusor overactivity in the male spontaneously hypertensive rat

• Published in: BJU international Vol. 110; no. 2b; pp. E118 - E124
• Main Authors: Inoue, Seiya, Saito, Motoaki, Tsounapi, Panagiota, Dimitriadis, Fotios, Ohmasa, Fumiya, Kinoshita, Yukako, Satoh, Keisuke, Takenaka, Atsushi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2012; Wiley Subscription Services, Inc
• Subjects: Administration, Oral; Adrenergic beta-1 Receptor Antagonists - administration & dosage; Adrenergic beta-1 Receptor Antagonists - pharmacology; Animals; bladder blood flow; calcitonin gene‐related peptide (CGRP); detrusor overactivity; Hypertension - complications; Indoles - administration & dosage; Indoles - pharmacology; Male; nerve growth factor (NGF); Rats; Rats, Inbred SHR; Rats, Wistar; Receptors, Adrenergic, beta-1 - metabolism; RNA, Messenger - metabolism; SHR; silodosin; Urinary Bladder - blood supply; Urinary Bladder, Overactive - drug therapy; Urinary Bladder, Overactive - etiology; Urinary Bladder, Overactive - physiopathology; Urination - physiology
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2011.10814.x

What's known on the subject? and What does the study add? Recently, several studies have suggested that detrusor overactivity (DO) is the result of bladder ischaemia. Hypertension could affect pelvic arterial blood flow, resulting in loss of smooth muscle in the bladder with resultant loss of bladder compliance. Spontaneously hypertensive rats are considered a valuable tool for exploring the pathogenesis of DO. Some reports indicate that α1 adrenoceptor antagonists improve chronic ischaemia of the lower urinary tract in patients with LUTS, with concomitant improvement of their symptoms as well as improvement of DO through an increased bladder blood flow (BBF) in the rat with bladder outlet obstruction. However, the mechanism of improvement of silodosin on storage or irritative symptoms is not well investigated and is still unclear. Silodosin prevents hypertension‐related DO in the SHR via several possible mechanisms. One possible mechanism of the efficacy of silodosin to the DO includes the improvement of the BBF. OBJECTIVE •  To investigate the effect of the α1A selective adrenoceptor antagonist, silodosin, on hypertension‐related detrusor overactivity (DO) and its possible mechanism in spontaneously hypertensive rats (SHRs). MATERIALS AND METHODS •  Twelve‐week‐old male SHRs received treatment with silodosin (100 µg/kg perorally) once daily for 6 weeks; vehicle‐treated Wistar rats and vehicle‐treated SHRs were used for our study. •  Six weeks after silodosin treatment, voiding functions were estimated by voiding behaviour and cystometric studies in all groups. •  The bladder blood flow was measured by the hydrogen clearance method, and tissue levels of nerve growth factor (NGF) and calcitonin gene‐related peptide (CGRP) were measured by enzyme‐linked immunosorbent assay (ELISA). •  Furthermore, the expressions of α1 adrenoceptor subtype mRNAs in the bladder were investigated by real‐time PCR method. RESULTS •  The SHRs showed significant increases in blood pressure, micturition frequency and tissue levels of NGF and CGRP in the bladder. •  Moreover, the SHRs showed significant decreases in bladder blood flow and single voided volume estimated by both voiding behaviour and cystometric studies compared with those in the Wistar rats. •  Six weeks of treatment with silodosin significantly ameliorated hypertension‐related alterations of these variables with concomitant small changes of blood pressure. •  The expression levels of α1 adrenoceptor subtype mRNAs in the bladder were similar in all the groups and the rank order was α1A =α1D > α1B in all groups. •  However, there were no significant differences in the expressions of α1A adrenoceptor mRNAs between any groups. CONCLUSION •  The data in the present study suggest that silodosin normalizes hypertension‐related DO in SHRs, which could be related to its effect on the increased blood flow in the bladder.