You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2010194 RHO-KINASE INHIBITION IMPACTS NEUROGENIC DETRUSOR OVERACTIVITY IN CHRONIC SPINALIZED RATS Dong Broqueres-You, Stephanie Oger, Delphine Behr-Roussel, Sandrine Compagnie, Stephanie Caisey, Pierre Denys, Emmanuel Chartier-Kastler, and Francois Giuliano Dong Broqueres-YouDong Broqueres-You Orsay, France More articles by this author , Stephanie OgerStephanie Oger Orsay, France More articles by this author , Delphine Behr-RousselDelphine Behr-Roussel Orsay, France More articles by this author , Sandrine CompagnieSandrine Compagnie Orsay, France More articles by this author , Stephanie CaiseyStephanie Caisey Orsay, France More articles by this author , Pierre DenysPierre Denys Garches, France More articles by this author , Emmanuel Chartier-KastlerEmmanuel Chartier-Kastler Paris, France More articles by this author , and Francois GiulianoFrancois Giuliano Garches, France More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.250AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Spinal cord injury (SCI) severely disrupts normal bladder function by inducing neurogenic detrusor overactivity (NDO). First line SCI-induced NDO treatments i.e. antimuscarinics often associated with intermittent catheterization are somewhat limited by a mild to moderate clinical efficacy and a significant incidence of side effects. Thus the development of new effective drugs for the treatment of NDO is of crucial importance. Rho-kinase has a central role in the regulation of detrusor smooth muscle contraction since components of the rhoA/rho-kinase signalling pathway are involved in the Ca2+-sensitization of the smooth muscle. Moreover, in vitro and in vivo data from animal models of overactive bladder (OAB) indicate that rho-kinases are involved in pathophysiological mechanisms responsible for OAB. Thus, we aimed to evaluate the effects of a rho-kinase inhibitor (Y-27632) on urodynamic parameters in rats with chronic SCI. METHODS Complete T7-T8 spinal cord transection was performed in 17 female adult Sprague-Dawley rats. At 3-4 weeks post-SCI, cystometry was performed in conscious rats to determine the effects of Y-27632 (150μg/kg, intravenous injection, iv, n=7) and vehicle (saline, iv, n=10) on the following urodynamic parameters: maximal amplitude of micturition pressure (MP); baseline intravesical pressure (BP); delta pressure threshold for inducing micturition (delta PT); intercontraction interval, (ICI); voided volume; amplitude of non-voiding contractions (NVC) and the volume threshold necessary to initiate NVC. The effects of Y-27632 or vehicle were observed during a treatment period of 60 min. The results were expressed as percentage of baseline value during the control period i.e before Y-27632 or saline injection. RESULTS Y-27632 significantly increased voided volume whereas it did not modify MP, BP, delta PT and ICI. Voided volume reached 117±9% of baseline at 60 min after Y-27632 injection versus 96±4% of baseline for vehicle. The amplitude of NVC was significantly decreased by 43.1% and 17.6% at 30 min and 60 min after Y-27632 administration, respectively when compared to vehicle. In addition, Y-27632 significantly increased the volume threshold of NVC. At 30 min and 60 min after Y-27632 injection, it was increased by 117.4% and by 166.3% when compared with vehicle. CONCLUSIONS The present study demonstrates that inhibition of rho-kinase alters the urodynamic parameters related to NVC and enables a better bladder emptying in SCI-induced NDO rats. This supports the potential development of rho-kinase inhibitors for the treatment of NDO. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e76-e77 Peer Review Report Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dong Broqueres-You Orsay, France More articles by this author Stephanie Oger Orsay, France More articles by this author Delphine Behr-Roussel Orsay, France More articles by this author Sandrine Compagnie Orsay, France More articles by this author Stephanie Caisey Orsay, France More articles by this author Pierre Denys Garches, France More articles by this author Emmanuel Chartier-Kastler Paris, France More articles by this author Francois Giuliano Garches, France More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...