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• W1991160490 abstract "You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2015PD7-07 A NOVEL TARGET FOR UNDERACTIVE BLADDER DISEASE: TRPV4 CATION CHANNEL ACTIVATION IMPROVES BLADDER FUNCTION IN A RAT MODEL FOR DETRUSOR UNDERACTIVITY Yves Deruyver, Emmanuel Weyne, Karel Dewulf, Wouter Everaerts, Thomas Voets, and Dirk De Ridder Yves DeruyverYves Deruyver More articles by this author , Emmanuel WeyneEmmanuel Weyne More articles by this author , Karel DewulfKarel Dewulf More articles by this author , Wouter EveraertsWouter Everaerts More articles by this author , Thomas VoetsThomas Voets More articles by this author , and Dirk De RidderDirk De Ridder More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.910AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Detrusor underactivity (DUA) is defined as a voiding contraction of reduced strength or duration resulting in bladder emptying problems. To date no effective therapeutic treatment exists for DUA. Earlier strategies have focused on increasing detrusor contractility. Novel stategies are trying to improve voiding efficacy by modulating the afferent nerves. Transient Receptor Potential channel Vanniloid 4 (TRPV4) is a key sensory protein in bladder urothelial cells that contributes to the detection of bladder filling. In addition, activation of TRPV4 on detrusor smooth muscle cells also improves detrusor contractility. We hypothetized that stimulation of TRPV4 would ameliorate cystometric parameters in a rat model for DUA. METHODS A total of 20 female Sprague-Dawley rats (10 weeks) underwent either bilateral preganglionic pelvic nerve crush (1x15s) or sham surgery under isoflurane anesthesia. Four weeks later awake cystometry was performed with infusion of saline and GSK1016790A (10 μM), a potent TRPV4 activator. RESULTS The mean intercontractile interval (ICI) and voided volume (VV) of pelvic nerve injured (PNI) rats increased almost threefold when compared to sham operated rats (respectively 140,3 vs. 377,3s and 0,27 vs. 0,82 ml). Also amplitude and peak pressure of voiding contractions were significantly decreased (53 vs. 13,95 cmH2O and 62,12 vs. 23,42 cmH2O). Intravesical instillation of GSK10167790A significantly shortened ICI (377,3s vs. 296,5s) and decreased VV (0,82 vs. 0,7 ml) in PNI rat, while voiding efficiency showed a trend towards improvement (72 vs. 82%, P=0,062). CONCLUSIONS PNI rats exhibit a cystometric phenotype characteristic of DUA. Activation of TRPV4 improves bladder function in this animal model for DUA through enhancement of afferent sensory pathways. The effect of TRPV4 activation on cystometric parameters seems to be more pronounced in PNI rats than in sham-operated rats. These findings make TRPV4 an interesting focus for pharmacological treatment of DUA. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e187 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yves Deruyver More articles by this author Emmanuel Weyne More articles by this author Karel Dewulf More articles by this author Wouter Everaerts More articles by this author Thomas Voets More articles by this author Dirk De Ridder More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ..." @default.
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• W1991160490 title "PD7-07 A NOVEL TARGET FOR UNDERACTIVE BLADDER DISEASE: TRPV4 CATION CHANNEL ACTIVATION IMPROVES BLADDER FUNCTION IN A RAT MODEL FOR DETRUSOR UNDERACTIVITY" @default.
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