PD24-02 ADDITIVE EFFECTS OF INTRAVENOUS AND INTRAVESICAL APPLICATION OF VIBEGRON, A β 3 -ADRENOCEPTOR AGONIST, ON BLADDER FUNCTION IN RATS WITH BLADDER OVERACTIVITY

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology II (PD24)1 Apr 2020PD24-02 ADDITIVE EFFECTS OF INTRAVENOUS AND INTRAVESICAL APPLICATION OF VIBEGRON, A β3-ADRENOCEPTOR AGONIST, ON BLADDER FUNCTION IN RATS WITH BLADDER OVERACTIVITY Akira Furuta*, Yasuyuki Suzuki, Taro Igarashi, Yusuke Koike, Shin Egawa, and Naoki Yoshimura Akira Furuta*Akira Furuta* More articles by this author , Yasuyuki SuzukiYasuyuki Suzuki More articles by this author , Taro IgarashiTaro Igarashi More articles by this author , Yusuke KoikeYusuke Koike More articles by this author , Shin EgawaShin Egawa More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000881.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Approximately 20% of oral intake of vibegron, a new β3-adrenoceptor agonist, is excreted into urine in the unchanged form. Therefore, we examined the effects of intravesical application of vibegron on bladder function in rats with oxotremorine methiodide (oxo-M: a nonselective muscarinic acetylcholine receptor agonist) -induced bladder overactivity. METHODS: Cystometry was performed in conscious female rats with intravesical instillation of oxo-M (200μM). In oxo-M-treated rats, vehicle or vibegron (1, 10mg/kg) was cumulatively administered intravenously at 30-minute intervals. In another group of rats, vehicle or vibegron (10, 100μM, 1mM) was cumulatively instilled intravesically at 60-minute intervals followed by intravenously application of vibegron (10mg/kg). Time-dependent changes in bladder function via cumulative intravenous or intravesical application of vehicle were also exmained. In addition, expression of β3-adrenoceptors (ARs) in the rat bladder was evaluated using immunohistochemical staining. RESULTS: Intravesical instillation of oxo-M induced bladder overactivity as evidenced by decreases in bladder capacity with increases in baseline, threshold and maximal voiding pressure. In oxo-M-treated rats, intravenous application of vibegron (10mg/kg) significantly increased bladder capacity (1.2 times) and decreased baseline, threshold and maximal voiding pressure compared with vehicle. Next, intravesical application of vibegron (1mM) significantly increased threshold pressure and bladder capacity (1.2 times) compared with vehicle. Combined treatments of intravesical (1mM) and intravenous (10mg/kg) application of vibegron induced a significantly larger rate of increases in bladder capacity (1.4 times) compared with vehicle although there were no significant time-dependent changes in bladder function. In addition, β3-ARs were expressed throughout the rat bladder, mainly in the urothelium. CONCLUSIONS: These results suggest that vibegron excreted into urine as the unchanged form induces the additive inhibitory effects on urinary frequency possibly by activating urothelial β3-ARs, which inhibits the afferent limb of micturition reflex rather than the efferent function evident as the increases in threshold pressure and bladder capacity without affecting bladder contractile function. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e532-e533 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Akira Furuta* More articles by this author Yasuyuki Suzuki More articles by this author Taro Igarashi More articles by this author Yusuke Koike More articles by this author Shin Egawa More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF downloadLoading ...