MP26-16 SUCCINATE IN VOIDING DYSFUNCTION ASSOCIATED WITH METABOLIC SYNDROME

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I1 Apr 2017MP26-16 SUCCINATE IN VOIDING DYSFUNCTION ASSOCIATED WITH METABOLIC SYNDROME Monica Velasquez Flores, Abubakr Mossa, Philippe Cammisotto, and Lysanne Campeau Monica Velasquez FloresMonica Velasquez Flores More articles by this author , Abubakr MossaAbubakr Mossa More articles by this author , Philippe CammisottoPhilippe Cammisotto More articles by this author , and Lysanne CampeauLysanne Campeau More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.787AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Disruption in energy homeostasis, the main factor driving metabolic syndrome, may also be responsible for the development of its associated bladder dysfunction. Succinate, an intermediate of the citric acid cycle, along with its receptor, GPR91, have been implicated in different aspects of metabolic syndrome, and it is possible that their role could extend to the bladder. Our goal is to show that succinate can alter bladder function in a model of bladder overactivity associated with metabolic syndrome. METHODS Intraperitoneal injections of saline or succinate were administered daily for a period of 4 weeks to Sprague-Dawley (SD) rats and Dahl/SS rats, a model of metabolic syndrome with hypertension. Succinate levels were measured in the plasma and urine. Conscious cystometry was then performed. On the next day, bladders were collected for organ bath experiments and quantitative PCR for GPR91. Bladder detrusor strips were stimulated with potassium chloride (KCl), carbachol, and electrical field stimulation (EFS). One-way ANOVA with Bonferroni post-hoc test was used to measure differences between all groups. P<0.05 was considered significant. RESULTS Dahl rats have lower plasma succinate levels compared to SD rats. 24-hour urine levels of succinate were increased in succinate-treated rats in both SD and Dahl groups. SD succinate-treated rats had significantly lower levels of GPR91 in the bladder compared to SD control rats. This was not observed in Dahl rats. Dahl rats had shorter intercontraction intervals, smaller bladder capacities and lower micturition volumes than SD rats. Chronic administration of succinate lowered these parameters, albeit not significant. Organ bath data showed that the contractile responses to KCl, carbachol and EFS were significantly increased in detrusor strips from Dahl control rats compared to those from the other three groups. CONCLUSIONS Models of metabolic syndrome have obvious differences in bladder function compared with control rats. Chronic administration of succinate, as observed in vitro, alters detrusor contractility of Dahl rats. The absence of down-regulation of GPR91 in the Dahl bladder treated with succinate could explain the alterations in detrusor contractility observed only in this group. Increased urinary succinate levels may contribute to the development of bladder dysfunction. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e325-e326 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Monica Velasquez Flores More articles by this author Abubakr Mossa More articles by this author Philippe Cammisotto More articles by this author Lysanne Campeau More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...