title: Chronic vardenafil treatment improves erectile function via structural maintenance of penile corpora cavernosa in rats with acute arteriogenic erectile dysfunction.
abstract: BACKGROUND
  Chronic phosphodiesterase type 5 inhibitor treatment may be useful in reversing erectile dysfunction (ED). However, the mechanisms of this improvement remain unknown.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Hospital Pharmacy-Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hotta
authors.forename: Mayuko
authors.initials: M
authors.lastname: Hattori
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kataoka
authors.forename: Risa
authors.initials: R
authors.lastname: Ohno
authors.forename: Mayumi
authors.initials: M
authors.lastname: Mikumo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018783:Impotence, Vasculogenic / Q000188:drug therapy*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000098:blood supply / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride
chemical_list: D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat