Prophylactic effect of tadalafil on bladder function in a rat model of chronic bladder ischemia

Masanori Nomiya*, David Mark Burmeister, Norifumi Sawada, Lysanne Campeau, Mona Zarifpour, Tristan Keys, Charles Peyton, Osamu Yamaguchi, Karl Erik Andersson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Purpose: We investigated the effect of tadalafil on chronic ischemia related bladder dysfunction. Materials and 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.

Original languageEnglish
Pages (from-to)754-761
Number of pages8
JournalJournal of Urology
Volume189
Issue number2
DOIs
StatePublished - Feb 2013
Externally publishedYes

Keywords

  • arterial occlusive diseases
  • ischemia
  • lower urinary tract symptoms
  • phosphodiesterase 5 inhibitors
  • urinary bladder

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