Effects of silodosin, a selective alpha-1A adrenoceptor antagonist, on erectile function in a rat model of partial bladder outlet obstruction

Neurourol Urodyn. 2017 Mar;36(3):597-603. doi: 10.1002/nau.23015. Epub 2016 Apr 6.

Abstract

Aim: We investigated the effects of silodosin (selective α1A -adrenoceptor antagonist) on erectile dysfunction (ED) in a rat model of bladder outlet obstruction.

Methods: Adult male Sprague-Dawley rats (n = 32) were divided into four groups: (i) sham-operated control; (ii) silodosin-treated (sham) control (0.1 mg/kg/day); (iii) partial bladder outlet obstruction (PBOO); and (iv) silodosin-treated with PBOO. PBOO was induced by ligation of the urethra for 6 weeks. In vivo, erectile responses were monitored by evaluating ratios of intracavernosal pressure (ICP)/mean arterial pressure (MAP). Organ-bath studies were performed on corpus cavernosum (CC) strips. Penises were assessed at baseline for protein expression of neuronal nitric oxide synthase (nNOS) and Rho-associated protein kinase (ROCK2) by Western blot. Immunohistochemistry and Masson trichrome staining were performed for analysis of nNOS protein levels and tissue alterations.

Results: The ratio of ICP/MAP was significantly decreased in obstructed rats (0.26 ± 0.043, P < 0.01) compared to sham-control rats (0.64 ± 0.10), which was restored by the treatment (0.59 ± 0.14, P < 0.01) compared with obstructed rats. Relaxation responses were significantly reduced in strips from the obstructed group. Silodosin restored nitrergic relaxant responses. nNOS expression in the obstructed group decreased, which was improved by treatment. The decreased smooth muscle/collagen ratio in the bladder obstructed group was reversed by the treatment.

Conclusions: Silodosin improves erectile function in obstructed rats. Further clinical trials are needed to explore fully the potential benefits of silodosin in patients with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in association with ED. Neurourol. Urodynam. 36:597-603, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: corpus cavernosum; direct noradrenergic response; partial bladder outlet obstruction; silodosin; α1A-adrenoceptor.

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / pharmacology
  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use*
  • Animals
  • Disease Models, Animal
  • Erectile Dysfunction / drug therapy*
  • Erectile Dysfunction / metabolism
  • Erectile Dysfunction / physiopathology
  • Indoles / pharmacology
  • Indoles / therapeutic use*
  • Male
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiopathology
  • Nitric Oxide Synthase Type I / metabolism
  • Penile Erection / drug effects*
  • Penis / drug effects
  • Penis / metabolism
  • Penis / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Urinary Bladder Neck Obstruction / drug therapy*
  • Urinary Bladder Neck Obstruction / metabolism
  • Urinary Bladder Neck Obstruction / physiopathology
  • Urological Agents / pharmacology
  • Urological Agents / therapeutic use*

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Indoles
  • Urological Agents
  • silodosin
  • Nitric Oxide Synthase Type I