title: Prophylactic effect of tadalafil on bladder function in a rat model of chronic bladder ischemia.
abstract: OBJECTIVE
  We investigated the effect of tadalafil on chronic ischemia related bladder dysfunction.
  
  
  METHODS
  Adult male Sprague-Dawley® rats were divided into control, arterial endothelial injury and arterial endothelial injury with tadalafil treatment groups. The arterial injury and arterial injury-tadalafil groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet after injury. Arterial injury-tadalafil rats received tadalafil (2 mg/kg per day) orally for 8 weeks after injury. The control group received a regular diet. At 8 weeks urodynamic investigation was performed. Bladder tissue was harvested for pharmacological studies, and histological examination of the iliac arteries and bladders was performed.
  
  
  RESULTS
  Iliac arteries from arterial injury and arterial injury-tadalafil rats showed neointimal formation and luminal occlusion. In the arterial injury group the micturition interval was significantly shorter (mean ± SEM 5.4 ± 0.5 vs 11.1 ± 1.1 minutes), and bladder capacity and voided volume were less than in controls. Contractile responses of bladder strips to KCl, electrical field stimulation and carbachol were significantly less after arterial injury than in controls. The arterial injury group showed a significantly increased percent of collagen compared with controls (mean 37.4% ± 1.8% vs 21.5% ± 1.8%). In the arterial injury-tadalafil group intimal formation and luminal occlusion were not prevented. However, there were significant improvements in all functional and morphological parameters compared with the arterial injury group.
  
  
  CONCLUSIONS
  Arterial occlusive disease may lead to chronic bladder ischemia and bladder hyperactivity. Chronic treatment with tadalafil protects bladder function and morphology, resulting in decreased bladder hyperactivity. If valid for humans, the data support phosphodiesterase 5 inhibition as treatment for chronic ischemia related bladder dysfunction.
authors.affiliation: Department of Urology, Fukushima Medical University School of Medicine, Fukushima City, Japan. mnomiya44@gmail.com
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomiya
authors.forename: David Mark
authors.initials: DM
authors.lastname: Burmeister
authors.forename: Norifumi
authors.initials: N
authors.lastname: Sawada
authors.forename: Lysanne
authors.initials: L
authors.lastname: Campeau
authors.forename: Mona
authors.initials: M
authors.lastname: Zarifpour
authors.forename: Tristan
authors.initials: T
authors.lastname: Keys
authors.forename: Charles
authors.initials: C
authors.lastname: Peyton
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000818:Animals; D002243:Carbolines / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D004195:Disease Models, Animal; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068581:Tadalafil; D001743:Urinary Bladder / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil