PD11-01 FAILURE OF ENHANCEMENT OF THE SOMATIC AND SYMPATHETIC NERVE INDUCED CONTINENCE REFLEX AFTER DULOXETINE, A NOREPINEPHRINE AND SEROTONIN REUPTAKE INHIBITOR, IN RATS WITH CEREBRAL INFARCTION (2014)

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Incontinence Evaluation1 Apr 2014PD11-01 FAILURE OF ENHANCEMENT OF THE SOMATIC AND SYMPATHETIC NERVE INDUCED CONTINENCE REFLEX AFTER DULOXETINE, A NOREPINEPHRINE AND SEROTONIN REUPTAKE INHIBITOR, IN RATS WITH CEREBRAL INFARCTION Minoru Miyazato, Takuma Oshiro, Ryo Namitome, Seiichi Saito, Michael Chancellor, William de Groat, and Naoki Yoshimura Minoru MiyazatoMinoru Miyazato More articles by this author , Takuma OshiroTakuma Oshiro More articles by this author , Ryo NamitomeRyo Namitome More articles by this author , Seiichi SaitoSeiichi Saito More articles by this author , Michael ChancellorMichael Chancellor More articles by this author , William de GroatWilliam de Groat More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.534AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Norepinephrine/serotonin reuptake inhibitors such as duloxetine have demonstrated clinical efficacy in the treatment of stress urinary incontinence (SUI). We have previously reported that duloxetine enhances the active urethral closure mechanism during sneezing that is mediated by somatic nerve-induced reflex contractions of external urethral sphincter via activation of both spinal noradrenergic and serotonergic systems in normal rats. However, it is not investigated whether these mechanisms are affected by cerebral infarction (CI). We therefore investigated the effect of duloxetine on the sneeze induced continence reflex as well as leak point pressure (LPP) in CI rats. METHODS The left middle cerebral artery was occluded with 4-0 nylon to create CI. (1) Three days later, sneeze-induced urethral responses were examined using a microtransducer-tipped catheter inserted to the middle urethra from the urethral orifice. Sneeze was induced by a rat′s whisker cut and inserted into the nostril under urethane anesthesia, and the effect of duloxetine (1 mg/kg, i.v.) on the amplitude of urethral responses during sneezing (A-URS) as well as urethral baseline pressure (UBP) was evaluated in normal and CI rats. (2) In normal and CI rats, LPP in the vertical tilt table preparation was measured under urethane anesthesia before and after duloxetine injection (1 mg/kg, i.v.). RESULTS (1) In CI rats, UBP was 43% lower (15.5 cm H2O) compared with normal rats (27.4 cm H2O), but A-URS did not differ in two groups (39.5 vs. 36.4 cm H2O). Duloxetine (i.v.) enhanced A-URS and UBP by 32% and 22%, respectively, in normal rats, but did not affect either in CI rats. (2) During passive intravesical pressure elevation, fluid leakage from the urethral meatus was observed at LPP of 35.8±4.5 cm H2O in CI rats, which was significantly lower compared with normal rats (56.9±6.6 cm H2O). Duloxetine increased LPP in normal rats up to 63.1±7.3 cm H2O, but not in CI rats. CONCLUSIONS In CI rats, the sneeze-induced urethral continence reflex is preserved, but urethral baseline pressure and tilt-LPP are lower than in normal rats, suggesting that CI might be a pathophysiological basis inducing SUI. Also the clinical efficacy of norepinephrine/serotonin reuptake inhibitors for SUI could be reduced in CI patients because duloxetine fails to activate spinal noradrenergic and/or serotonergic systems controlling the pudendal nerve induced urethral continence reflex and sympathetic nerve-dependent UBP in CI. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e286 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Minoru Miyazato More articles by this author Takuma Oshiro More articles by this author Ryo Namitome More articles by this author Seiichi Saito More articles by this author Michael Chancellor More articles by this author William de Groat More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...