一氧化氮介导人食管下括约肌舒张的作用机制

目的 探讨一氧化氮在人食管下括约肌（LES）舒张中的作用,比较其对钩状纤维和套索纤维的不同作用。方法 选用32例高位食管癌切除术LES标本,分离钩状纤维和套索纤维,在离体条件下行电场刺激（EFS）。并比较一氧化氮合酶（NOS）抑制剂N^G-硝基-L-精氨酸（L-NNA）、NOS底物L-精氨酸、神经毒河豚毒素（TTX）、阿托品的不同影响。做硝普钠对两肌条的浓度效应曲线。结果 EFS能诱导钩状纤维和部分套索纤维产生频率依赖性舒张。L-NNA能抑制此作用,并可被L-精氨酸部分逆转。钩状纤维和套索纤维的最大舒张频率分别为512Hz和16Hz。EFS也能诱导部分套索纤维和钩状纤维引起撤收缩反应。EFS能诱导另一部分套索纤维收缩反应,可被阿托品抑制,其最大收缩频率为128Hz。TTX可完全消除EFS诱导的反应,硝普钠能引起与EFS相似的反应。结论在LES离体实验状态下,EFS诱导钩状纤维和套索纤维的舒张与L-NNA、TTX及硝普钠有关,可能是由一氧化氮介导的。但两束肌纤维对EFS反应不同,高频刺激时套索纤维舒张幅度较大,低频刺激时钩状纤维舒张幅度大。EFS还诱导部分套索纤维产生收缩反应。

Mechanism of relaxation mediated by nitric oxide on human lower esophageal sphincter

OBJECTIVE: To explore the mechanism of relaxation mediated by nitric oxide on the human lower esophageal sphincter (LES), and compare the difference in relaxation response between clasp fibers and sling fibers. METHODS: 32 LES specimens were obtained from 32 patients with high-positioned carcinoma of the mid-esophagus, 12 males and 16 females, aged 55.9 +/- 9.3, during operation. The clasp fibers and sling fibers were isolated and suspended in perfusion tough. Electric field stimulation (EFS) was applied to the clasp and sling fibers in vitro. Nitric oxide synthase (NOS) inhibitor L-NNA, NOS substrate L-arginine, neurotoxin tetrodotoxin (TTX), and atropine were added respectively to observe their effects on the clasp and sling fibers under EFS. Sodium nitroprusside was added on the two kinds of smooth muscle stripes to observe its influence as well. RESULTS: EFS induced frequency-dependent relaxation to clasp fibers and some of sling fibers, which was inhibited by L-NNA in a concentration-dependent manner and was reversed by L-arginine partially. Maximal relaxation in clasp fibers and sling fibers was observed at 512 Hz and 16 Hz respectively. The higher amplitude relaxation was induced in the sling fibers at lower stimulus frequencies (< 32 Hz). Conversely, the same response was induced in the clasp fibers at higher stimulus frequencies (> 64 Hz). Meanwhile, off-contraction was induced by EFS in some sling fibers and clasp fibers. In some sling fibers, contraction was induced by EFS which was inhibited by atropine. Maximal contraction in these fibers was observed at 128 Hz. TTX abolished the effect of EFS on both clasp and sling fibers, which was considered neurogenic. Sodium nitroprusside elicited the similar response to EFS. CONCLUSIONS: Relaxation of clasp and sling fibers is related to L-NNA, TTX, and sodium nitroprusside, and can be mediated by nitric oxide. Lower stimulus frequencies induce higher amplitude relaxation to sling fibers, and conversely, higher stimulus frequencies induce higher amplitude relaxation to clasp fibers. EFS induces contraction response in some sling fibers.