Reitz André, Bretscher Sibylle, Knapp Peter A, Müntener Michael, Wefer Björn, Schurch Brigitte
Neuro-Urology, Swiss Paraplegic Center, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland.
Eur Urol. 2004 Mar;45(3):367-73. doi: 10.1016/j.eururo.2003.10.002.
This functional urodynamic study assessed the effect of the nitric oxide donor isosorbide dinitrate on the external urethral sphincter and hypothesised first that nitric oxide could lower the resting sphincter pressure, second that nitric oxide could influence the sphincter contractility during magnetic stimulation, and third that nitric oxide could induce a faster external urethral sphincter fatigue during continuous magnetic stimulation.
Eight healthy males gave their written informed consent and were included. A 2-channel microtip pressure transducer catheter was inserted into the urethra measuring the bladder and the external urethral sphincter pressure. Magnetic stimulation of the sacral roots was performed to evoke reproducible contractions of the external urethral sphincter. The baseline protocol included six single pulse stimulations and three stimulations 10sec in duration each for two frequencies 5Hz and 50Hz with intensities at the motor threshold of the pelvic floor. Then the subjects received 10 mg of isosorbide nitrate sublingually and the protocol was repeated 5min, 20min, 40min and 60min after drug administration.
The sublingual administration of isosorbide dinitrate could significantly reduce the resting pressure of the external urethral sphincter for at least one hour. The maximal contractile strength measured as the maximal urethral pressure during single pulse and continuous magnetic stimulation of the sacral roots also decreased significantly. Nitric oxide did not induce a significantly faster fatigue of the external urethral sphincter during continuous magnetic stimulation of the sacral roots.
This study shows a functionally relevant effect of nitric oxide on the resting tone and the contractile behaviour of the human external urethral sphincter in vivo while the fatigue properties did not changed significantly. Nitric oxide donors could offer a new pharmacological approach to treat urinary retention due to overactive or non-relaxing external urethral sphincter.
本功能性尿动力学研究评估了一氧化氮供体硝酸异山梨酯对外尿道括约肌的影响，并提出以下假设：其一，一氧化氮可降低括约肌静息压力；其二，一氧化氮可在磁刺激期间影响括约肌收缩力；其三，一氧化氮可在连续磁刺激期间诱导外尿道括约肌更快疲劳。
八名健康男性签署书面知情同意书后纳入研究。将一根双通道微尖端压力传感器导管插入尿道，测量膀胱和外尿道括约肌压力。对骶神经根进行磁刺激，以诱发可重复的外尿道括约肌收缩。基线方案包括六次单脉冲刺激和三次持续10秒的刺激，频率分别为5Hz和50Hz，强度为盆底运动阈值。然后受试者舌下含服10mg硝酸异山梨酯，并在给药后5分钟、20分钟、40分钟和60分钟重复该方案。
舌下含服硝酸异山梨酯可使外尿道括约肌静息压力显著降低至少一小时。在对骶神经根进行单脉冲和连续磁刺激期间，以最大尿道压力衡量的最大收缩强度也显著降低。在对骶神经根进行连续磁刺激期间，一氧化氮并未诱导外尿道括约肌明显更快疲劳。
本研究表明，一氧化氮对人体外尿道括约肌的静息张力和收缩行为具有功能上相关的影响，而疲劳特性未发生显著变化。一氧化氮供体可为治疗因外尿道括约肌过度活跃或不松弛导致的尿潴留提供一种新的药理学方法。
