PD24-01 NITRIC OXIDE CENTRALLY INDUCES FREQUENT URINATION VIA BRAIN GLUTAMATERGIC RECEPTORS IN RATS

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology II (PD24)1 Apr 2020PD24-01 NITRIC OXIDE CENTRALLY INDUCES FREQUENT URINATION VIA BRAIN GLUTAMATERGIC RECEPTORS IN RATS Hideaki Ono, Takahiro Shimizu*, Suo Zou, Masaki Yamamoto, Yohei Shimizu, Yurika Hata, Shogo Shimizu, Youichirou Higashi, Takaaki Aratake, Tomoya Hamada, Yoshiki Nagao, Masashi Honda, and Motoaki Saito Hideaki OnoHideaki Ono More articles by this author , Takahiro Shimizu*Takahiro Shimizu* More articles by this author , Suo ZouSuo Zou More articles by this author , Masaki YamamotoMasaki Yamamoto More articles by this author , Yohei ShimizuYohei Shimizu More articles by this author , Yurika HataYurika Hata More articles by this author , Shogo ShimizuShogo Shimizu More articles by this author , Youichirou HigashiYouichirou Higashi More articles by this author , Takaaki AratakeTakaaki Aratake More articles by this author , Tomoya HamadaTomoya Hamada More articles by this author , Yoshiki NagaoYoshiki Nagao More articles by this author , Masashi HondaMasashi Honda More articles by this author , and Motoaki SaitoMotoaki Saito More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000881.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In the lower urinary tract, nitric oxide (NO) is well known as a relaxation factor in the urethra. On the other hand, in the central nervous system, NO is reported to have both inhibitory and facilitatory effects on the micturition reflex. We previously reported that intracerebroventricularly (icv) administered SIN-1, a NO donor, reduced intercontraction intervals (ICI), single voided volume and bladder capacity without altering post-voided residual urine volume, indicating that SIN-1 centrally induced frequent urination in rats. In this study, we examined central mechanisms for the SIN-1-induced frequent urination focusing on glutamatergic receptors (NMDA and AMPA types) in rats. METHODS: Urethane anesthetized (0.8 g/kg, ip) male Wistar rats (300-450 g) were used. A catheter was inserted into the bladder from the dome to perform cystometrograms (CMG, 12 ml/h saline infusion). Three hours after the surgery, SIN-1 (100 or 250 μg/rat) or vehicle was icv administered. In some rats, carboxy-PTIO (PTIO, NO scavenger, 750 μg/rat), MK-801 (NMDA type glutamatergic receptor antagonist, 10 or 30 nmol/rat) or DNQX (AMPA type glutamatergic receptor antagonist, 3 nmol/rat) was administered 30 min before SIN-1 administration (250 μg/rat, icv). CMG and evaluation of ICI and maximal voiding pressure (MVP) were started 60 min before the first icv administration. RESULTS: Icv administered SIN-1 dose-dependently reduced ICI compared with the vehicle-administered control group without altering MVP (Fig. 1). The SIN-1-induced ICI reduction was significantly attenuated by central pretreatment with PTIO or MK-801 (Fig. 2A and 2B), but not by DNQX (data not shown). CONCLUSIONS: NO centrally induces frequent urination via brain NMDA, but not AMPA, type glutamatergic receptors in rats. Thus, the brain nitrergic pathway that is directly involved in the control of micturition could be a new target for the treatment of bladder dysfunction. Source of Funding: JSPS KAKENHI (#17K09303), Narishige Neuroscience Research Foundation in Japan, Takeda Science Foundation, The Smoking Research Foundation in Japan © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e532-e532 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hideaki Ono More articles by this author Takahiro Shimizu* More articles by this author Suo Zou More articles by this author Masaki Yamamoto More articles by this author Yohei Shimizu More articles by this author Yurika Hata More articles by this author Shogo Shimizu More articles by this author Youichirou Higashi More articles by this author Takaaki Aratake More articles by this author Tomoya Hamada More articles by this author Yoshiki Nagao More articles by this author Masashi Honda More articles by this author Motoaki Saito More articles by this author Expand All Advertisement PDF downloadLoading ...