You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research II1 Apr 2015MP12-17 PROTECTIVE EFFECT OF A RHO-KINASE INHIBITOR ON CHRONIC ISCHEMIA-RELATED BLADDER DYSFUNCTION Hidenori Akaihata, Masanori Nomiya, Nobuhiro Haga, Nobuhiro Kushida, Kei Ishibashi, Ken Aikawa, Osamu Yamaguchi, and Yoshiyuki Kojima Hidenori AkaihataHidenori Akaihata More articles by this author , Masanori NomiyaMasanori Nomiya More articles by this author , Nobuhiro HagaNobuhiro Haga More articles by this author , Nobuhiro KushidaNobuhiro Kushida More articles by this author , Kei IshibashiKei Ishibashi More articles by this author , Ken AikawaKen Aikawa More articles by this author , Osamu YamaguchiOsamu Yamaguchi More articles by this author , and Yoshiyuki KojimaYoshiyuki Kojima More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.792AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent studies have suggested that aging-associated changes in pelvic vasculature such as atherosclerosis eventually result in chronic bladder ischemia, which may play a key role in the development of lower urinary tract symptoms. Currently, it has been shown that the RhoA/Rho-kinase (ROK) pathway is substantially involved in the pathogenesis of atherosclerosis. On the other hand, there are many studies reporting that alteration of the RhoA/ROK pathway is at least partly involved in bladder overactivity. However, it has not been established whether inhibition of the RhoA/ROK pathway affects chronic ischemia-related bladder dysfunction. The aim of study is to investigate the effect of fasudil, a ROK inhibitor, on chronic ischemia-related bladder dysfunction by using a rat model of chronic bladder ischemia. METHODS Adult Sprague-Dawley male rats (16 weeks old) were divided into control, arterial endothelial injury (AI), and AI with fasudil treatment (AI/Fa) groups. The AI group underwent balloon endothelial injury of bilateral iliac arteries and received a 2 percent cholesterol diet for 8 weeks to induce chronic bladder ischemia. The AI/Fa group was given fasudil (30 mg/kg/day) orally once daily after arterial endothelial injury and received a 2 percent cholesterol diet for 8 weeks. The control group received a regular diet for 8 weeks. After cystometrogram (CMG) recording, the bladders and common iliac arteries were harvested for pharmacological and histological examinations. RESULTS The mean arterial wall thickness of the common iliac arteries was significantly greater in the AI group than in the control group. The collagen ratio in the muscle layer in the AI group was significantly increased as compared with the control group. In the organ bath study, contractile responses of muscle strips to various stimuli were significantly less in the AI group than in the control group. In the CMG, the micturition interval was significantly shorter in the AI group than in the control group. In the AI/Fa group, arterial wall thickening was significantly suppressed compared with the AI group. The collagen ratio in the muscle layer was significantly decreased in AI/Fa group as compared with AI group. Furthermore, significant improvements were seen in muscle strip contractility and cystometric parameters in the AI/Fa group compared with the AI group. CONCLUSIONS The present results suggest that chronic treatment with fasudil may prevent neointimal formation and chronic ischemia-related bladder dysfunction, resulting in improvement of bladder hyperactivity. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e134 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hidenori Akaihata More articles by this author Masanori Nomiya More articles by this author Nobuhiro Haga More articles by this author Nobuhiro Kushida More articles by this author Kei Ishibashi More articles by this author Ken Aikawa More articles by this author Osamu Yamaguchi More articles by this author Yoshiyuki Kojima More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...