Bennett B C, Kruse M N, Roppolo J R, Flood H D, Fraser M, de Groat W C
Division of Urology, University of Pittsburgh, Pennsylvania 15213, USA.
J Urol. 1995 Jun;153(6):2004-9.
The present study investigated the role of nitric oxide (NO) in the reflex changes in urethral outlet activity during micturition. Isovolumetric bladder contractions, urethral pressure and external urethral sphincter electromyogram (EUS EMG) activity were recorded independently in urethane-anesthetized rats. During reflex bladder contractions, the urethra exhibited reflex responses characterized by an initial decrease in urethral pressure in conjunction with a rise in bladder pressure. This was followed by a period of high frequency oscillations (HFOs) associated with maximal urethral relaxation and burst type EUS EMG activity. Administration of N-nitro-L-arginine (L-NOARG) 10 mg./kg. intravenously, a nitric oxide synthase inhibitor, reversibly decreased the magnitude (62%, p < 0.05) and duration (40%, p < 0.05) of reflex urethral relaxation (N = 7). In 4 additional experiments, L-NOARG (10 to 15 mg./kg. intravenously) completely eliminated reflex urethral relaxation during micturition, and this effect was reversed in all animals by the administration of L-arginine (100 to 150 mg./kg. intravenously). Administration of N-nitro-D-arginine (D-NOARG) (10 to 30 mg./kg. intravenously) had no effect on reflex urethral relaxation. Neuromuscular blockade (vecuronium bromide 5 mg./kg. intravenously) reversibly decreased resting urethral pressure and eliminated the HFOs. The urethral smooth muscle relaxation that remained after neuromuscular blockade was eliminated following administration of L-NOARG (10 mg./kg. intravenously) in 2 of 3 animals. These results suggest that reflex urethral responses during micturition involve changes in both smooth and striated muscle activity, and that the predominant neurotransmitter mechanisms that mediate reflex urethral smooth muscle relaxation involve NO.
本研究调查了一氧化氮（NO）在排尿过程中尿道出口活动反射性变化中的作用。在氨基甲酸乙酯麻醉的大鼠中，分别记录等容膀胱收缩、尿道压力和尿道外括约肌肌电图（EUS EMG）活动。在反射性膀胱收缩期间，尿道表现出反射性反应，其特征为尿道压力最初下降，同时膀胱压力升高。随后是一段高频振荡（HFOs）时期，与最大程度的尿道松弛和爆发型EUS EMG活动相关。静脉注射10mg/kg的一氧化氮合酶抑制剂N-硝基-L-精氨酸（L-NOARG），可使反射性尿道松弛的幅度（62%，p<0.05）和持续时间（40%，p<0.05）可逆性降低（N=7）。在另外4个实验中，L-NOARG（静脉注射10至15mg/kg）完全消除了排尿期间的反射性尿道松弛，并且在所有动物中，通过静脉注射L-精氨酸（100至150mg/kg）可逆转这种作用。静脉注射N-硝基-D-精氨酸（D-NOARG）（10至30mg/kg）对反射性尿道松弛无影响。神经肌肉阻滞（静脉注射5mg/kg维库溴铵）可使静息尿道压力可逆性降低，并消除HFOs。在3只动物中的2只，静脉注射L-NOARG（10mg/kg）后，神经肌肉阻滞后剩余的尿道平滑肌松弛被消除。这些结果表明，排尿期间的反射性尿道反应涉及平滑肌和横纹肌活动的变化，并且介导反射性尿道平滑肌松弛的主要神经递质机制涉及NO。
