MP60-07 BRAIN CARBON MONOXIDE SUPPRESSES THE RAT MICTURITION VIA BRAIN GABA RECEPTORS

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP60-07 BRAIN CARBON MONOXIDE SUPPRESSES THE RAT MICTURITION VIA BRAIN GABA RECEPTORS Masaki Yamamoto, Takahiro Shimizu, Suo Zou, Shogo Shimizu, Youichirou Higashi, Mikiya Fujieda, and Motoaki Saito Masaki YamamotoMasaki Yamamoto More articles by this author , Takahiro ShimizuTakahiro Shimizu More articles by this author , Suo ZouSuo Zou More articles by this author , Shogo ShimizuShogo Shimizu More articles by this author , Youichirou HigashiYouichirou Higashi More articles by this author , Mikiya FujiedaMikiya Fujieda More articles by this author , and Motoaki SaitoMotoaki Saito More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003318.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Carbon monoxide (CO) is a well-known toxic gas but is also reported as a gasotransmitter besides nitric oxide and hydrogen sulfide. Endogenous CO is produced by heme oxygenase (HO)-induced heme catabolism and shows physiological functions such as anti-inflammation and neuromodulation. In this study, we examined effects of centrally administered CORM3 (CO donor) and ZnPP (HO inhibitor) on the rat micturition. METHODS: Urethane anesthetized (0.8 g/kg, ip) male Wistar rats (350-450 g) were used. A catheter was inserted into the bladder to perform continuous cystometry (12 ml/h saline infusion). Three hours after the surgery, CORM3 (1 or 10 nmol/rat), ZnPP (10 or 30 nmol/rat) or vehicle was intracerebroventricularly (ICV) administered. In some rats, effects of ICV pretreated SR95531 (SR, GABAA antagonist, 0.1 nmol/rat) on the CORM3 (10 nmol/rat, ICV)-induced responses were examined. Continuous cystometry and evaluation of intercontraction intervals (ICI) and maximal voiding pressure (MVP) were started 30 min before the first ICV administration. In some rats, before and after ZnPP administration (30 nmol/rat, ICV), single cystometry (12 ml/h saline infusion) was performed. RESULTS: CORM3 dose-dependently prolonged ICI without changing MVP (Figure 1A-B). On the other hand, ZnPP dose-dependently shortened ICI without changing MVP (Figure 1C-D). In single cystometry, ZnPP significantly reduced single-voided volume and bladder capacity without changing post-voiding residual volume (Table 1). The ZnPP (30 nmol/rat, ICV)-induced ICI shortening was reversed in the central presence of CORM3 (10 nmol/rat, ICV) (Figure 2). The CORM-3-induced ICI prolongation was suppressed by SR (Figure 3). CONCLUSIONS: Brain CO endogenously suppresses the rat micturition via brain GABAA receptors. Thus, the brain CO might be a new therapeutic target for neurogenic bladder overactivity. Source of Funding: JSPS KAKENHI (#21K09428, #20K07827) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e845 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masaki Yamamoto More articles by this author Takahiro Shimizu More articles by this author Suo Zou More articles by this author Shogo Shimizu More articles by this author Youichirou Higashi More articles by this author Mikiya Fujieda More articles by this author Motoaki Saito More articles by this author Expand All Advertisement PDF downloadLoading ...