Rattan S, Chakder S
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Am J Physiol. 1992 Jan;262(1 Pt 1):G107-12. doi: 10.1152/ajpgi.1992.262.1.G107.
The studies were performed in in vitro to examine the role of nitric oxide (NO) in nonadrenergic noncholinergic (NANC) nerve-mediated relaxation of the internal anal sphincter (IAS) smooth muscle strips of opossums. NO caused a concentration-dependent fall in the resting tension of the IAS. The inhibitory action of NO may be exerted directly on the IAS smooth muscle since it was not modified by the neurotoxin tetrodotoxin (1 x 10(-6) M), which abolished the neurally mediated fall in the IAS tension. The inhibitor of NO synthesis NG-nitro-L-arginine (L-NNA) produced concentration-dependent suppression of the neurally mediated fall in the IAS tension. The suppression of the neurally mediated IAS relaxation was stereoselective because D-NNA had no effect on the control responses. The suppressant action of L-NNA was selectively reversed by L-arginine in a concentration-dependent manner. The reversal was complete with 3 x 10(-4) M L-arginine. D-Arginine on the other hand, at the same concentration had no effect on L-NNA-suppressed IAS relaxation. Interestingly, the fall in the IAS tension caused by vasoactive intestinal polypeptide (VIP) (an inhibitory neurotransmitter in the IAS) was also inhibited by L-NNA (3 x 10(-5) M). From these data we conclude that NO or NO-like substances serve as important inhibitory mediators for the NANC nerve-mediated IAS relaxation. A part of the inhibitory action of VIP on the IAS involves NO-synthase pathway. The exact site of formation and release of NO or NO-like substances in response to NANC nerve stimulation remain to be investigated.
这些研究在体外进行，以检验一氧化氮（NO）在负鼠肛门内括约肌（IAS）平滑肌条非肾上腺素能非胆碱能（NANC）神经介导的舒张中的作用。NO导致IAS静息张力呈浓度依赖性下降。NO的抑制作用可能直接作用于IAS平滑肌，因为它不受神经毒素河豚毒素（1×10⁻⁶ M）的影响，河豚毒素消除了神经介导的IAS张力下降。NO合成抑制剂NG-硝基-L-精氨酸（L-NNA）对神经介导的IAS张力下降产生浓度依赖性抑制。对神经介导的IAS舒张的抑制具有立体选择性，因为D-NNA对对照反应无影响。L-NNA的抑制作用可被L-精氨酸以浓度依赖性方式选择性逆转。3×10⁻⁴ M的L-精氨酸可完全逆转。另一方面，相同浓度的D-精氨酸对L-NNA抑制的IAS舒张无影响。有趣的是，血管活性肠肽（VIP，IAS中的一种抑制性神经递质）引起的IAS张力下降也被L-NNA（3×10⁻⁵ M）抑制。从这些数据我们得出结论，NO或NO样物质是NANC神经介导的IAS舒张的重要抑制介质。VIP对IAS的部分抑制作用涉及NO合酶途径。响应NANC神经刺激时NO或NO样物质的确切形成和释放部位仍有待研究。
