Kakizaki H, de Groat W C
Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
J Urol. 1996 Jan;155(1):355-60.
Nitric oxide (NO) is known to have an important transmitter function at peripheral synapses in the urogenital tract and has also been implicated in the transmission of nociceptive information in the spinal cord. The present study evaluated the role of NO in the central micturition reflex pathway.
We examined the effect of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, on micturition reflexes induced by continuous infusion of saline or 0.1% acetic acid (a noxious stimulus) into the bladder in urethane-anesthetized female rats. Bladder and external urethral sphincter function were monitored with a continuous cystometrogram (CMG) and electromyography (EMG).
Intrathecal injection of L-NAME (0.01 to 1 mumol.) did not significantly change the CMG or sphincter EMG during saline infusion. Infusion of acetic acid decreased the intercontraction interval (ICI), indicating a decrease in the volume threshold for inducing micturition. Subsequent intrathecal administration of L-NAME partially reversed the decreased ICI in a dose-dependent manner, but did not change the amplitude of bladder contractions: 0.01, 0.1 and 1 mumol. of L-NAME produced increases of 25%, 31% and 56% in the ICI. D-NAME, the inactive stereoisomer had no effect. This effect of L-NAME was reversed by injection of L-arginine (2 mumol. intrathecally) which, by itself, did not alter ICI during saline infusion or acetic acid infusion.
These results indicate that: (1) spinal NO containing pathways do not play a role in the normal micturition reflex, (2) NO is involved at the spinal level in the facilitation of the micturition reflex by nociceptive bladder afferents activated by noxious chemical irritation of the bladder.
已知一氧化氮（NO）在泌尿生殖道的外周突触中具有重要的递质功能，并且也与脊髓中伤害性信息的传递有关。本研究评估了NO在中枢排尿反射通路中的作用。
我们在氨基甲酸乙酯麻醉的雌性大鼠中，研究了NO合酶抑制剂N-硝基-L-精氨酸甲酯（L-NAME）对通过向膀胱持续输注生理盐水或0.1%乙酸（一种伤害性刺激）诱导的排尿反射的影响。通过连续膀胱测压图（CMG）和肌电图（EMG）监测膀胱和尿道外括约肌功能。
鞘内注射L-NAME（0.01至1μmol）在输注生理盐水期间未显著改变CMG或括约肌EMG。输注乙酸可缩短收缩间期（ICI），表明诱导排尿的容量阈值降低。随后鞘内给予L-NAME以剂量依赖性方式部分逆转了ICI的降低，但未改变膀胱收缩的幅度：0.01、0.1和1μmol的L-NAME使ICI分别增加25%、31%和56%。无活性的立体异构体D-NAME没有作用。鞘内注射L-精氨酸（2μmol）可逆转L-NAME的这种作用，而L-精氨酸本身在输注生理盐水或乙酸期间不会改变ICI。
这些结果表明：（1）含脊髓NO的通路在正常排尿反射中不起作用；（2）NO在脊髓水平参与由膀胱有害化学刺激激活的伤害性膀胱传入神经对排尿反射的促进作用。
