Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 201225 THE FATTY ACID AMIDE HYDROLASE INHIBITOR OLEOYL ETHYL AMIDE INCREASES BLADDER STORAGE CAPACITY AND REDUCES DETRUSOR OVERACTIVITY IN RATS Giorgio Gandaglia, Frank Strittmatter, Fabio Benigni, Giovanni La Croce, Marco Moschini, Christian Stief, Patrizio Rigatti, Christian Gratzke, Francesco Montorsi, and Petter Hedlund Giorgio GandagliaGiorgio Gandaglia Milan, Italy More articles by this author , Frank StrittmatterFrank Strittmatter Munich, Germany More articles by this author , Fabio BenigniFabio Benigni Milan, Italy More articles by this author , Giovanni La CroceGiovanni La Croce Milan, Italy More articles by this author , Marco MoschiniMarco Moschini Milan, Italy More articles by this author , Christian StiefChristian Stief Munich, Germany More articles by this author , Patrizio RigattiPatrizio Rigatti Milan, Italy More articles by this author , Christian GratzkeChristian Gratzke Munich, Germany More articles by this author , Francesco MontorsiFrancesco Montorsi Milan, Italy More articles by this author , and Petter HedlundPetter Hedlund Milan, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.068AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The endocannabinoid system may be a pharmacological target for lower urinary tract symptoms. Fatty acid amide hydrolase (FAAH) degrades endocannabinoids and has been located to the human and rat urothelium. Acute FAAH-inhibition modifies urodynamic parameters in rats. The aim of our study was to evaluate the effect by chronic treatment with oleoyl ethyl amide (OEtA), a FAAH-inhibitor, on bladder function and detrusor overactivity (DO) in female rats. METHODS After ethical approval, 19 female Sprague-Dawley rats were given daily subcutaneous OEtA 0.3mg/kg (n=11), or vehicle (n=8). After two weeks, bladder function and responses to intravesical PGE2 (50uM) were assessed with cystometry. Isolated bladders were prepared for organbath studies of responses to nerve activation and carbachol (1nM-0.1mM). Values are mean±SEM. Statistical methods were t-test and ANOVA. RESULTS Bladder and body weights were similar in both groups. At baseline, micturition interval (MI) and volume (MV) were 6.8±0.2 and 4.3±0.3 minutes and 1.1±0.03 and 0.6±0.05 ml for OEtA and control rats (p<0.01). Treated rats had lower residual volume (RV). Bladder capacity (BC) was 1.1±0.03 and 0.7±0.05 ml for OEtA and controls (p<0.01). No differences were noted for basal pressure (BP), maximum pressure (MP) or area under the curve (AUC). Threshold pressure (TP) and flow pressure (FP) were higher (p<0.05) in treated rats (21±0.3 and 36±0.6) vs. controls (16±0.5 and 26±0.6 cmH2O). After PGE2, MI, MV and RV amounted to 5.3±0.1 (OEtA) and 2.9±0.2 minutes (controls; p<0.01), 0.9±0.03 ml (OEtA) and 0.4±0.03 ml (controls; p<0.01), and 0.03±0.003 ml (OEtA) and 0.06±0.007 ml (controls; p<0.05) and BC was 0.9±0.03 ml (OEtA) and 0.5±0.02 ml (controls; p<0.01). Increases in BP and AUC to PGE2 were larger in controls (45%±4% and 52%±3%) than OEtA rats (15%±1% and 31%±1%; p<0.05). In treated rats, FP increased 18%±1% to 42±1.0 cmH2O after PGE2 whereas no change was observed in controls (p<0.01). In organbath experiments, at low concentrations of carbachol (10nM-100nM) detrusor from treated rats responded with larger (p<0.05) contractions than controls, but no differences in Emax were recorded. Nerve-induced contractions were similar in both groups. CONCLUSIONS Chronic OEtA-treatment affects sensory urodynamic parameters, increases bladder storage capacity and reduces DO. A role for FAAH and the endocannabinoid system in urinary bladder function and dysfunction may be considered. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byFüllhase C, Russo A, Castiglione F, Benigni F, Campeau L, Montorsi F, Gratzke C, Bettiga A, Stief C, Andersson K and Hedlund P (2018) Spinal Cord FAAH in Normal Micturition Control and Bladder Overactivity in Awake RatsJournal of Urology, VOL. 189, NO. 6, (2364-2370), Online publication date: 1-Jun-2013. Volume 187Issue 4SApril 2012Page: e10 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giorgio Gandaglia Milan, Italy More articles by this author Frank Strittmatter Munich, Germany More articles by this author Fabio Benigni Milan, Italy More articles by this author Giovanni La Croce Milan, Italy More articles by this author Marco Moschini Milan, Italy More articles by this author Christian Stief Munich, Germany More articles by this author Patrizio Rigatti Milan, Italy More articles by this author Christian Gratzke Munich, Germany More articles by this author Francesco Montorsi Milan, Italy More articles by this author Petter Hedlund Milan, Italy More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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