PMID- 32558992 OWN - NLM STAT- MEDLINE DCOM- 20210325 LR - 20210325 IS - 1520-6777 (Electronic) IS - 0733-2467 (Linking) VI - 39 IP - 6 DP - 2020 Aug TI - Brain nitric oxide induces facilitation of the micturition reflex through brain glutamatergic receptors in rats. PG - 1687-1699 LID - 10.1002/nau.24440 [doi] AB - AIM: Brain nitric oxide (NO) have been reported in regulation of the sympatho-adrenomedullary system, which can affect voiding and storage functions. Therefore, we investigated effects of intracerebroventricularly (icv) administered 3-(4-morpholinyl)sydnonimine, hydrochloride (SIN-1) (NO donor) on the micturition reflex, focusing on their dependence on the sympatho-adrenomedullary system and on brain N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors in urethane-anesthetized (0.8 g/kg, ip) male Wistar rats. METHODS: Plasma noradrenaline and adrenaline were measured just before and 5 minutes after SIN-1 administration. Evaluation of urodynamic parameters was started 1 hour before SIN-1 administration or intracerebroventricular pretreatment with other drugs. RESULTS: SIN-1 (100 and 250 microg/animal) elevated plasma adrenaline and reduced intercontraction interval ([ICI] values; 110.5% [SIN-1, 0 microg] and 54.9% [SIN-1, 250 microg] during 15 minutes after SIN-1 administration [P < .05; eta(2) = 0.59]) without affecting plasma noradrenaline or maximal voiding pressure. SIN-1 (250 microg/animal) reduced single-voided volume and bladder capacity without affecting post-voiding residual volume. The SIN-1 (250 microg/animal)-induced adrenaline elevation and ICI reduction were attenuated by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, sodium salt (carboxy-PTIO) (NO scavenger, icv) (ICI values; 44.7% [vehicle + SIN-1] and 77.5% [carboxy-PTIO + SIN-1] during 15 minutes after SIN-1 administration [P < .05; eta(2) = 0.51]). Acute bilateral adrenalectomy abolished SIN-1-induced adrenaline elevation, while showed no effect on the SIN-1-induced ICI reduction. The ICI reduction was attenuated by MK-801 (NMDA receptor antagonist, icv) (ICI values; 47.0% [vehicle + SIN-1] and 87.6% [MK-801 + SIN-1] during 15 minutes after SIN-1 administration [P < .05; eta(2) = 0.61]), but not by DNQX (AMPA receptor antagonist, icv). CONCLUSION: Brain NO is involved in facilitation of the rat micturition reflex through brain NMDA receptors, independently of the sympatho-adrenomedullary outflow modulation. CI - (c) 2020 Wiley Periodicals LLC. FAU - Ono, Hideaki AU - Ono H AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. AD - Innovative Medicine Group, Center for Innovative and Translational Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. FAU - Shimizu, Takahiro AU - Shimizu T AUID- ORCID: 0000-0002-1555-2284 AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. FAU - Zou, Suo AU - Zou S AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. FAU - Yamamoto, Masaki AU - Yamamoto M AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. FAU - Shimizu, Yohei AU - Shimizu Y AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. AD - Innovative Medicine Group, Center for Innovative and Translational Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. FAU - Aratake, Takaaki AU - Aratake T AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. AD - Research Fellow of Japan Society for the Promotion of Science, Japan. FAU - Hamada, Tomoya AU - Hamada T AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. FAU - Nagao, Yoshiki AU - Nagao Y AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. FAU - Shimizu, Shogo AU - Shimizu S AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. FAU - Higashi, Youichirou AU - Higashi Y AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. FAU - Saito, Motoaki AU - Saito M AUID- ORCID: 0000-0002-2962-1607 AD - Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200619 PL - United States TA - Neurourol Urodyn JT - Neurourology and urodynamics JID - 8303326 RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Nitric Oxide Donors) RN - 0 (Quinoxalines) RN - 0 (Receptors, AMPA) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 31C4KY9ESH (Nitric Oxide) RN - 5O5U71P6VQ (linsidomine) RN - 62T278S1MX (FG 9041) RN - 6LR8C1B66Q (Dizocilpine Maleate) RN - D46583G77X (Molsidomine) RN - X4W3ENH1CV (Norepinephrine) RN - YKH834O4BH (Epinephrine) SB - IM MH - Animals MH - Brain/*drug effects/metabolism MH - Dizocilpine Maleate/pharmacology MH - Epinephrine/blood MH - Excitatory Amino Acid Antagonists/pharmacology MH - Male MH - Molsidomine/analogs & derivatives/pharmacology MH - Nitric Oxide/*metabolism MH - Nitric Oxide Donors/pharmacology MH - Norepinephrine/blood MH - Quinoxalines/pharmacology MH - Rats MH - Rats, Wistar MH - Receptors, AMPA/*metabolism MH - Receptors, N-Methyl-D-Aspartate/*metabolism MH - Reflex/drug effects/physiology MH - Urination/*drug effects/physiology OTO - NOTNLM OT - NMDA receptors OT - brain OT - glutamate OT - micturition reflex OT - nitric oxide EDAT- 2020/06/20 06:00 MHDA- 2021/03/26 06:00 CRDT- 2020/06/20 06:00 PHST- 2020/04/07 00:00 [received] PHST- 2020/05/28 00:00 [revised] PHST- 2020/06/08 00:00 [accepted] PHST- 2020/06/20 06:00 [pubmed] PHST- 2021/03/26 06:00 [medline] PHST- 2020/06/20 06:00 [entrez] AID - 10.1002/nau.24440 [doi] PST - ppublish SO - Neurourol Urodyn. 2020 Aug;39(6):1687-1699. doi: 10.1002/nau.24440. Epub 2020 Jun 19.