Masuda Hitoshi, Ogawa Teruyuki, Kihara Kazunori, Chancellor Michael B, de Groat William C, Yoshimura Naoki
Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
BJU Int. 2007 Jul;100(1):175-80. doi: 10.1111/j.1464-410X.2007.06872.x. Epub 2007 May 4.
To investigate the effects of anaesthesia on the nitrergic pathway during the micturition reflex in rats.
The effects of N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on bladder and urethral activities were evaluated by infusion cystometrography (CMG) and urethral perfusion pressure under isovolumetric conditions in awake or urethane-anaesthetized rats. L-NAME was administered intravenously (i.v.), intrathecally (i.t.), intracerebroventriculary (i.c.v.) or intravesically in normal rats or rats pre-treated with resiniferatoxin, a potent C-fibre afferent neurotoxin.
L-NAME injected i.v. decreased the intercontraction interval (ICI) in the awake but increased it in the anaesthetized rats. L-NAME injected i.t. increased the ICI in both states and these effects were not apparent after pre-treatment with resiniferatoxin. L-NAME injected i.c.v. decreased the ICI in the awake but increased i.t. in the anaesthetized rats. Intravesical L-NAME decreased the ICI in the awake but not in the anaesthetized rats. L-NAME administered i.v., but not i.t. or i.c.v., increased bladder contraction during CMG. Under isovolumetric conditions, L-NAME administered i.v., but not i.t. or i.c.v., reduced the urethral relaxation without changing bladder contraction.
These results indicate that spinal NO release facilitates the mechanoceptive C-fibres, and this facilitatory effect is masked by supraspinal (possibly forebrain) and local inhibitory effects of NO during the micturition reflex in awake rats. Urethane seems to inhibit the supraspinal and local inhibitory effects of NO, resulting in unmasking the facilitatory effect of NO in the spinal cord and brain stem. During the voiding phase, urethral relaxation depends on the peripheral but not the central NO system.
研究麻醉对大鼠排尿反射过程中氮能通路的影响。
通过在清醒或氨基甲酸乙酯麻醉的大鼠等容条件下进行灌注膀胱测压（CMG）和尿道灌注压力，评估一氧化氮（NO）合酶抑制剂N(G)-硝基-L-精氨酸甲酯（L-NAME）对膀胱和尿道活动的影响。L-NAME通过静脉内（i.v.）、鞘内（i.t.）、脑室内（i.c.v.）或膀胱内给药，给药对象为正常大鼠或用强效C纤维传入神经毒素树脂毒素预处理的大鼠。
静脉注射L-NAME可缩短清醒大鼠的收缩间期（ICI），但延长麻醉大鼠的收缩间期。鞘内注射L-NAME在两种状态下均延长ICI，且在用树脂毒素预处理后这些作用不明显。脑室内注射L-NAME可缩短清醒大鼠的ICI，但延长麻醉大鼠的ICI。膀胱内注射L-NAME可缩短清醒大鼠的ICI，但对麻醉大鼠无效。静脉注射L-NAME（而非鞘内或脑室内注射）可增加CMG期间的膀胱收缩。在等容条件下，静脉注射L-NAME（而非鞘内或脑室内注射）可降低尿道松弛而不改变膀胱收缩。
这些结果表明，脊髓中NO的释放促进机械感受性C纤维，并且在清醒大鼠排尿反射过程中，这种促进作用被NO的脊髓上（可能是前脑）和局部抑制作用所掩盖。氨基甲酸乙酯似乎抑制了NO的脊髓上和局部抑制作用，从而使脊髓和脑干中NO的促进作用得以显现。在排尿期，尿道松弛依赖于外周而非中枢NO系统。
