MP85-03 THE THERAPEUTIC EFFECT OF TRPV4 ACTIVATION IN THE BLADDER ON UNDERACTIVE BLADDER IN RATS WITH PELVIC NERVE CRUSH

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction I1 Apr 2017MP85-03 THE THERAPEUTIC EFFECT OF TRPV4 ACTIVATION IN THE BLADDER ON UNDERACTIVE BLADDER IN RATS WITH PELVIC NERVE CRUSH Ei-ichiro Takaoka, Shun Takai, Takahisa Suzuki, Nobutaka Shimizu, Joonbeom Kwon, Hiroki Okada, Hiroyuki Nishiyama, Naoki Yoshimura, and Christopher J. Chermansky Ei-ichiro TakaokaEi-ichiro Takaoka More articles by this author , Shun TakaiShun Takai More articles by this author , Takahisa SuzukiTakahisa Suzuki More articles by this author , Nobutaka ShimizuNobutaka Shimizu More articles by this author , Joonbeom KwonJoonbeom Kwon More articles by this author , Hiroki OkadaHiroki Okada More articles by this author , Hiroyuki NishiyamaHiroyuki Nishiyama More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Christopher J. ChermanskyChristopher J. Chermansky More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2665AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Incomplete bladder emptying due to detrusor underactivity (DU) is a significant urological problem underlying underactive bladder (UAB). Also, TRPV4 has been reported to be one of the mechanosensitive channels expressed in the bladder. In this study, we sought to produce a consistent rat model of UAB with the modification of our previous model of pelvic nerve crush (PNC) (2016 AUA) and evaluated the therapeutic effect of intravesical application of a TRPV4 agonist on the UAB condition. METHODS In female Sprague-Dawley rats, the visceral branches of bilateral pelvic nerves were identified near the internal iliac vessels and bilateral PNC was made by two times of nerve compression of either side with each 20-seconds duration using sharp forceps. After 10 days, awake cystometrograms (CMG) were recorded in sham control and PNC rats. Then, in both groups, a TRPV4 agonist (GSK1016790A) was continuously administered into the bladder and the CMG parameters were compared before and after intravesical drug administration. RESULTS The bladder weight was significantly increased in PNC rats vs. control rats. In CMG, PNC rats showed significant increases in voided volume, post-void residual urine volume, and residual urine rate compared to control rats. PNC rats also revealed the significant increases in intercontraction intervals (ICI), a number of non-voiding contractions, and threshold pressure while the amplitude during voiding was significantly decreased (table). In the TRPV4 administration study, intravesical application of 1.5µM of GSK 1016790A significantly decreased ICI, voided volume, and post-void residual urine volume in PNC rats while it did not significantly affect any CMG parameters in control rats. CONCLUSIONS Rats with pelvic nerve injury induced by the modified PNC method, which showed the characteristics of DU, seem to be an appropriate model for evaluation of peripheral neurogenic mechanisms of UAB. Also TRPV4 that reduced the bladder capacity and residual urine volume could be a potential target for the treatment of UAB. © 2017FiguresReferencesRelatedDetailsCited byKaplan S (2017) Re: Qualitative Exploration of the Patient Experience of Underactive BladderJournal of Urology, VOL. 199, NO. 3, (588-589), Online publication date: 1-Mar-2018. Volume 197Issue 4SApril 2017Page: e1148-e1149 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ei-ichiro Takaoka More articles by this author Shun Takai More articles by this author Takahisa Suzuki More articles by this author Nobutaka Shimizu More articles by this author Joonbeom Kwon More articles by this author Hiroki Okada More articles by this author Hiroyuki Nishiyama More articles by this author Naoki Yoshimura More articles by this author Christopher J. Chermansky More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...