Chronic vardenafil treatment improves erectile function via structural maintenance of penile corpora cavernosa in rats with acute arteriogenic erectile dysfunction

J Sex Med. 2011 Mar;8(3):705-11. doi: 10.1111/j.1743-6109.2010.02153.x. Epub 2010 Dec 8.

Abstract

Introduction: Chronic phosphodiesterase type 5 inhibitor treatment may be useful in reversing erectile dysfunction (ED). However, the mechanisms of this improvement remain unknown.

Aim: The aim of this article was to determine the mechanisms of the improvement by chronic vardenafil treatment for acute arteriogenic ED in rats.

Methods: Eight-week-old male Wistar-ST rats were divided into four groups: sham-operated rats (Control group) and rats with acute arteriogenic ED induced by ligating bilateral internal iliac arteries (Ligation group), subsequently treated with low-dose (0.4 mg/kg/day; VL group) or high-dose (4.0 mg/kg/day; VH group) vardenafil for 20 days from 1 week after ligature.

Main outcome measures: Erectile function was assessed based on changes of intracavernous pressure (ICP) followed by electrostimulation of the cavernous nerves and was evaluated by the area under the curve of ICP/area under the curve of mean arterial pressure (area of ICP/MAP). Transforming growth factor (TGF)-β(1), vascular endothelial growth factor-A, endothelial nitric oxide synthase (eNOS), inducible NOS, and neuronal NOS mRNA expression levels in penile corpus cavernosum were determined by real-time PCR. Western blotting for TGF-β(1) protein levels and Masson trichrome staining of penile tissues were performed in each at group 4 weeks after surgery.

Results: In the VH group, area of ICP/MAP was significantly improved when compared with the Ligation group (P < 0.01). The smooth muscle (SM)/collagen ratio in the VH group was significantly higher than in the Ligation group (P < 0.05), and was comparable with that in the Control group. TGF-β(1) mRNA and protein levels in the VH group were significantly lower when compared with the Ligation group (P < 0.05).

Conclusions: Chronic vardenafil administration ameliorates impairment of penile hemodynamics and maintains normal SM to collagen ratio in cavernous tissues after acute arterial injury in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Disease Models, Animal
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology*
  • Imidazoles / therapeutic use
  • Impotence, Vasculogenic / drug therapy*
  • Male
  • Nitric Oxide Synthase Type II / metabolism
  • Penile Erection / drug effects*
  • Penis / blood supply
  • Penis / drug effects
  • Phosphodiesterase 5 Inhibitors / pharmacology*
  • Phosphodiesterase 5 Inhibitors / therapeutic use
  • Piperazines / administration & dosage
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfones / administration & dosage
  • Sulfones / pharmacology
  • Sulfones / therapeutic use
  • Triazines / administration & dosage
  • Triazines / pharmacology
  • Triazines / therapeutic use
  • Vardenafil Dihydrochloride

Substances

  • Imidazoles
  • Phosphodiesterase 5 Inhibitors
  • Piperazines
  • Sulfones
  • Triazines
  • Vardenafil Dihydrochloride
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat