脑内一氧化氮通过大鼠脑内谷氨酸能受体诱导排尿反射易化。

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

机构信息

Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.

Innovative Medicine Group, Center for Innovative and Translational Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.

出版信息

Neurourol Urodyn. 2020 Aug;39(6):1687-1699. doi: 10.1002/nau.24440. Epub 2020 Jun 19.

DOI:10.1002/nau.24440

PMID:32558992

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 = 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 = 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 = 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.

摘要

目的

据报道，脑内一氧化氮（NO）参与调节交感肾上腺髓质系统，从而影响排尿和储存功能。因此，我们研究了脑室（icv）给予 3-（4-吗啉基）-4-亚硝基哌啶盐酸盐（SIN-1）（NO 供体）对排尿反射的影响，重点研究其对交感肾上腺髓质系统以及脑内 N-甲基-D-天冬氨酸（NMDA）和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的依赖性，在氯醛糖麻醉（0.8 g/kg，ip）雄性 Wistar 大鼠中。

方法

在给予 SIN-1 前后立即测量血浆去甲肾上腺素和肾上腺素。在 SIN-1 给药前 1 小时或通过脑室预处理其他药物开始评估尿动力学参数。

结果

SIN-1（100 和 250 µg/动物）升高了血浆肾上腺素并缩短了收缩间期（[ICI]值；SIN-1 给药后 15 分钟内 110.5%[SIN-1，0 µg]和 54.9%[SIN-1，250 µg][P<.05；η=0.59]），而不影响血浆去甲肾上腺素或最大排尿压。SIN-1（250 µg/动物）降低了单次排尿量和膀胱容量，而不影响排尿后残余量。SIN-1（250 µg/动物）引起的肾上腺素升高和 ICI 降低被 2-（4-羧基苯基）-4,4,5,5-四甲基咪唑啉-1-氧-3-氧化物，钠盐（羧基-PTIO）（NO 清除剂，icv）减弱（ICI 值；SIN-1 给药后 15 分钟内 44.7%[载体+SIN-1]和 77.5%[羧基-PTIO+SIN-1][P<.05；η=0.51]）。急性双侧肾上腺切除术消除了 SIN-1 引起的肾上腺素升高，但对 SIN-1 引起的 ICI 降低没有影响。ICI 降低被 MK-801（NMDA 受体拮抗剂，icv）减弱（ICI 值；SIN-1 给药后 15 分钟内 47.0%[载体+SIN-1]和 87.6%[MK-801+SIN-1][P<.05；η=0.61]），但不受 DNQX（AMPA 受体拮抗剂，icv）影响。