1514 CEREBRAL INFARCTION FAILS TO ENHANCE THE SNEEZE-INDUCED CONTINENCE REFLEX AFTER DULOXETINE, A NOREPINEPHRINE AND SEROTONIN REUPTAKE INHIBITOR, IN RATS

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Incontinence - Evaluation & Therapy I1 Apr 20101514 CEREBRAL INFARCTION FAILS TO ENHANCE THE SNEEZE-INDUCED CONTINENCE REFLEX AFTER DULOXETINE, A NOREPINEPHRINE AND SEROTONIN REUPTAKE INHIBITOR, IN RATS Minoru Miyazato, Yasuhiro Kaiho, Hideaki Izumi, Naoki Kawamorita, Haruo Nakagawa, Yoichi Arai, Michael Chancellor, William de Groat, and Naoki Yoshimura Minoru MiyazatoMinoru Miyazato Pittsburgh, PA More articles by this author , Yasuhiro KaihoYasuhiro Kaiho Miyagi, Japan More articles by this author , Hideaki IzumiHideaki Izumi Miyagi, Japan More articles by this author , Naoki KawamoritaNaoki Kawamorita Miyagi, Japan More articles by this author , Haruo NakagawaHaruo Nakagawa Miyagi, Japan More articles by this author , Yoichi AraiYoichi Arai Miyagi, Japan More articles by this author , Michael ChancellorMichael Chancellor Royal Oak, MI More articles by this author , William de GroatWilliam de Groat Pittsburgh, PA More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2358AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Norepinephrine and 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 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 bladder function 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. (2) In normal and CI rats, continuous cystometry was evaluated before and after duloxetine injection. 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 cm H2O 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) CI reduced intercontraction intervals without affecting the amplitude of bladder contractions compared with normal rats. Duloxetine prolonged intercontraction intervals in CI rats, but not in normal rats. CONCLUSIONS In CI rats, the sneeze-induced urethral continence reflex is preserved, but urethral baseline pressure is lower compared with normal rats. Duloxetine improves urinary frequency but fails to enhance the sneeze-induced urethral responses (both A-URS and UBP) after CI. These results suggest that: (1) CI induces not only bladder overactivity, but also SUI, which may account for mixed incontinence in CI patients, and (2) norepinephrine and serotonin reuptake inhibition is effective to treat bladder overactivity, but not for SUI due to failed activation of spinal noradrenergic and/or serotonergic systems controlling the urethral continence reflex in CI. Thus, the clinical efficacy of norepinephrine/serotonin reuptake inhibitors for SUI could be reduced in SUI patients with CI while they are useful for the treatment of overactive bladder. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e584 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Minoru Miyazato Pittsburgh, PA More articles by this author Yasuhiro Kaiho Miyagi, Japan More articles by this author Hideaki Izumi Miyagi, Japan More articles by this author Naoki Kawamorita Miyagi, Japan More articles by this author Haruo Nakagawa Miyagi, Japan More articles by this author Yoichi Arai Miyagi, Japan More articles by this author Michael Chancellor Royal Oak, MI More articles by this author William de Groat Pittsburgh, PA More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...