Silodosin improves functional consequences of lower urinary tract obstruction secondary to benign prostate hypertrophy, a proof of concept study in the spontaneously hypertensive rat supplemented with testosterone

BMC Urol. 2020 Aug 27;20(1):132. doi: 10.1186/s12894-020-00699-y.

Abstract

Background: The main purpose of this study is to investigate the effect of silodosin on the urodynamic consequences in a previously established model of lower urinary tract symptoms associated with benign prostate hyperplasia, the spontaneously hypertensive rats (SHR) supplemented with testosterone.

Methods: Three groups of animals (8-week-old; n = 10/group) were considered: Wistar Kyoto (control) rats (WKY), SHR supplemented with testosterone at 3 mg/kg/day and treated with either vehicle (SHR-T, n = 10) or silodosin at 0.1 mg/kg/day (SHR-T + silodosin, n = 10) by oral gavage for 6 weeks. Cystometry experiments were performed. The bladder was harvested, weighed and paraffin-embedded for morphometric analysis. The prostate was also harvested and weighed.

Results: The number of animals included in the analysis were n = 10/10 for WKY and n = 7-8/10 for each SHR rats supplemented with testosterone group. SHR-T displayed a significant decrease in the intercontraction interval, infused volume and mean flow rate whereas the frequency of non-voiding contractions was increased. Silodosin improved the voiding behavior of SHR-T by significantly increasing the intercontraction interval, the infused volume and the mean flow rate and decreasing the number of non-voiding contractions. SHR-T displayed a significant increase in prostate and bladder weights and a 15% increase in the detrusor wall area compared to WKY.

Conclusions: Chronic silodosin treatment relieved storage symptoms in SHR supplemented with testosterone and decreased the frequency of non-voiding detrusor contractions during the filling phase.

Keywords: Benign prostatic hyperplasia; Bladder function; Experimental cystometry; Lower urinary tract obstruction; Silodosin; Spontaneously hypertensive rats.

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use*
  • Animals
  • Indoles / therapeutic use*
  • Male
  • Proof of Concept Study
  • Prostatic Hyperplasia / complications
  • Prostatic Hyperplasia / drug therapy*
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Testosterone / therapeutic use*
  • Treatment Outcome
  • Urinary Bladder Neck Obstruction / drug therapy*
  • Urinary Bladder Neck Obstruction / etiology

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Indoles
  • Testosterone
  • silodosin