Brain nitric oxide induces facilitation of the micturition reflex through brain glutamatergic receptors in rats

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; η2 = 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; η2 = 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; η2 = 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.

Psychological/mental stress‐induced effects on urinary function: Possible brain molecules related to psychological/mental stress‐induced effects on urinary function

“…4), which abolished the SIN-1-induced plasma adrenaline elevation in rats. 139 Since Masuda et al reported that centrally administered L-NAME (NO synthase inhibitor) inhibited micturition in anesthetized rats, 140 our data in anesthetized rats show that brain NO can induce frequent urination, independently of the sympathoadrenomedullary outflow, a representative stress response.…”

“…4), and reduced BC and SVV without changing RV, and the SIN‐1‐induced ICI shortening was not influenced by ADX (Fig. 4), which abolished the SIN‐1‐induced plasma adrenaline elevation in rats 139 . Since Masuda et al .…”

“…At a dose that showed no effect on micturition in rats, central pretreatment with MK-801 (NMDA receptor antagonist), but not DNQX (AMPA receptor antagonist), attenuated the centrally administered SIN-1-induced ICI shortening in rats. 139 Therefore, brain NO might be involved in the facilitation of micturition in rats through the brain glutamatergic nervous system.…”

“…* P < 0.05 versus vehicle. Reproduced from Ono et al 139 . with permission from John Wiley and Sons.…”