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Brain nitric oxide induces facilitation of the micturition reflex through brain glutamatergic receptors in rats
Author(s) -
Ono Hideaki,
Shimizu Takahiro,
Zou Suo,
Yamamoto Masaki,
Shimizu Yohei,
Aratake Takaaki,
Hamada Tomoya,
Nagao Yoshiki,
Shimizu Shogo,
Higashi Youichirou,
Saito Motoaki
Publication year - 2020
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.24440
Subject(s) - medicine , nitric oxide , endocrinology , urination , nmda receptor , reflex , anesthesia , receptor , urinary system
Abstract 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 α ‐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 µg/animal) elevated plasma adrenaline and reduced intercontraction interval ([ICI] values; 110.5% [SIN‐1, 0 µg] and 54.9% [SIN‐1, 250 µg] during 15 minutes after SIN‐1 administration [ P < .05; η 2 = 0.59]) without affecting plasma noradrenaline or maximal voiding pressure. SIN‐1 (250 µg/animal) reduced single‐voided volume and bladder capacity without affecting post‐voiding residual volume. The SIN‐1 (250 µg/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; η 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; η 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.