254 MODULATION OF THE URETHRAL CLOSURE REFLEX DURING SNEEZING BY SPINAL CHOLINERGIC PATHWAYS IN RATS

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2012254 MODULATION OF THE URETHRAL CLOSURE REFLEX DURING SNEEZING BY SPINAL CHOLINERGIC PATHWAYS IN RATS Satoru Yoshikawa and Naoki Yoshimura Satoru YoshikawaSatoru Yoshikawa 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.2012.02.311AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Stress urinary incontinence (SUI) is defined as involuntary leakage of urine under abdominal stress conditions such as sneezing. Previous studies reported that the urethral closure reflex (UCR) during sneezing is a crucial defense mechanism preventing urinary leakage, and that both noradrenergic and serotonergic pathways in the sacral spinal cord contribute to the UCR. However, a role of cholinergic pathways in the UCR has not been elucidated. We therefore investigated the effect of intrathecal (i.t.) administration of an acetylcholine (ACh) esterase inhibitor, which increases ACh in the synaptic terminal, and anti-cholinergic agents on the UCR in rats. METHODS In female SD rats, sneeze reflex was induced by their whisker cut and inserted into the nostril under urethane anesthesia. Urethral responses were measured using a mirotransducer-tipped catheter inserted into the middle urethra from the urethral orifice. An ACh esterase inhibitor (neostigmine: 0.1-3 nmol, i.t.) was administered at the level of L6-S1 spinal cord, and then the changes in amplitudes of urethral responses during sneezing (A-URS) and urethral basal pressure (UBP) were recorded. A muscarinic receptor blockers (atropine: 0.03-3 nmol) or a nicotinic receptor blocker (mecamylamine: 30 nmol) were also administered i.t. before the administration of neostigmine (3 nmol, i.t.). RESULTS Neostigmine dose-dependently and significantly decreased A-URS at all doses tested with approximately 70% reduction at 3 nmol (Fig. A). However, there was no change in UBP. (Fig. B). The neostigmine (3 nmol)-induced decrease in A-URS was dose-dependently reversed by atropine (non-selective antagonist) compared to the vehicle group(p<0.05) (Fig. C). Mecamylamine showed a tendency for suppression of neostigmine effects without statistical significance compared to the vehicle group. On the other hand, none of muscarinic or nicotinic blockers by themselves induced any significant changes in either A-URS or UBP. CONCLUSIONS These data indicate that an increase in endogenous ACh at the sacral spinal cord inhibits the UCR as shown by a decrease in A-URS during sneezing via activation of muscarinic receptors. These new findings may imply that enhancement of the spinal cholinergic function could be involved in the pathological mechanism inducing SUI. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e103 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Satoru Yoshikawa Pittsburgh, PA More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...