You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology (MP08)1 Sep 2021MP08-17 ALTERED CALCIUM SIGNALING AND SERCA DYSFUNCTION CONTRIBUTE TO BLADDER DYSFUNCTION IN METABOLIC SYNDROME Leo Song, John Strobel, James Byrd, Mouhamad Alloosh, Michael Sturek, and CR Powell Leo SongLeo Song More articles by this author , John StrobelJohn Strobel More articles by this author , James ByrdJames Byrd More articles by this author , Mouhamad AllooshMouhamad Alloosh More articles by this author , Michael SturekMichael Sturek More articles by this author , and CR PowellCR Powell More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001981.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder dysfunction in metabolic syndrome (MetS) remains poorly understood despite being one of its most common complications. We hypothesize that bladder dysfunction in chronic, late stage MetS results in underactive bladder driven in part by sarcoendoplasmic reticulum calcium transport ATPase (SERCA) dysfunction. METHODS: Age matched Ossabaw pig models of MetS were fed a hypercaloric, atherogenic diet for 12 months to induce MetS and compared with control pigs. Urodynamic parameters were obtained in-vivo. Detrusor smooth muscle (DSM) cells were enzymatically isolated and intracellular Ca2+ handling was interrogated with fura-2. RESULTS: MetS was confirmed by obesity, hypertension, serum glucose, and increased total and LDL cholesterol (n=2). MetS exhibited inhibited SERCA activity based on less rapid and less vigorous “undershoot” during recovery of the intracellular Ca2+ response to caffeine (5.6±5 vs -10.8±4, p=0.03). As SERCA is the primary driver for Ca2+ recovery, impaired SERCA is a potential cause of subsequent bladder dysfunction. MetS also exhibited a trend toward increased response to carbachol 10µM but not 1µM (72.5±26 vs 47.8±16 cmH2O, p=0.08) and no difference in bladder pressure at capacity compared to controls (n=2). CONCLUSIONS: This pilot study indicates that DSM from MetS pigs demonstrates decreased SERCA activity, highlighting a potential therapeutic target for bladder dysfunction in MetS. This is the first time SERCA dysfunction has been demonstrated in MetS DSM. Source of Funding: This project was supported by a Project Development Team within the ICTSI NIH/NCRR Grant Number RR025761 (Powell, PI) and NIDDK DiaComp Pilot & Feasibility project, sub-award DK076169 (Powell, PI) and NIH grant HL062552 (Sturek, PI), NIH UL1 RR025761 (Sturek, CO-I), NIH P30 DK097512 (Sturek Co-I), Indiana University MedSTAR program (Song) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e157-e157 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Leo Song More articles by this author John Strobel More articles by this author James Byrd More articles by this author Mouhamad Alloosh More articles by this author Michael Sturek More articles by this author CR Powell More articles by this author Expand All Advertisement Loading ...