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

Abstract

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. 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. 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 adrenalectomyabolished 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). Brain NO is involved in facilitation of the rat micturition reflex through brain NMDA receptors, independently of the sympatho-adrenomedullary outflow modulation.