内源性一氧化氮在哮喘大鼠气道高反应性中的作用

目的　利用一氧化氮合成前体Ｌ精氨酸（ＬＡｒｇ） 和一氧化氮合酶抑制剂亚硝基Ｌ精氨酸甲酯（ＬＮＡＭＥ）研究内源性一氧化氮在哮喘大鼠气道高反应性中的作用，探讨支气管哮喘的发病机制。方法　用卵白蛋白作为致敏原制备哮喘大鼠模型，建立大鼠离体气管环张力的测定方法，并用ＬＡｒｇ、ＬＮＡＭＥ和ＬＡｒｇ＋ ＬＮＡＭＥ孵育离体气管环，观察气管环乙酰胆碱浓度反应曲线和最大收缩反应的变化，同时观察去上皮对哮喘大鼠气道反应性的影响。结果　哮喘大鼠（１０ 只） 离体气管环经ＬＮＡＭＥ１０５ ｍｏｌ／Ｌ孵育后对乙酰胆碱的最大收缩反应从孵育前（１２４±３９） ｍｇ 上升到（１８７ ±５３） ｍｇ，孵育前、后最大收缩反应比较差异具有显著性（ Ｐ＜ ０．０１），浓度反应曲线上移，而ＬＡｒｇ 可以逆转ＬＮＡＭＥ的作用，单用ＬＡｒｇ ２×１０５ ｍｏｌ／Ｌ和ＬＡｒｇ１０３ ｍｏｌ／Ｌ孵育气管环，对哮喘大鼠气管环的最大收缩反应和浓度反应曲线与对照组比较，差异无显著性（ Ｐ＞ ０．０５） 。去上皮哮喘大鼠气管环的反应性与上皮完整气管环比较差异有显著性（ Ｐ＜ ０．００５） ，而ＬＡｒｇ、ＬＮＡＭＥ＋ ＬＡｒｇ 和ＬＮＡＭＥ孵育去上

The role of endogenous nitric oxide in airway hyperresponsiveness of asthmatic rats

OBJECTIVE: Nitric oxide (NO) precursor L-arginine (L-Arg) and NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) were used to investigate the role of endogenous NO in airway hyperresponsiveness of asthmatic rats. METHODS: Asthmatic wistar rats were developed by sensitization and challenging with ovalbumin. Airway responsivess to acetylcholine (Ach) was measured in vitro in isolated and perfused rat tracheal rings with or without epithelium after inhibiting or stimulating NO synthesis. RESULTS: After asthmatic rat tracheal rings were incubated in vitro with L-NAME 10(-5) mol/L, the maximal response of tracheal rings to Ach was increased compared with that of the control group. When asthmatic rat tracheal rings were coincubated with L-Arginine 2 x 10(-5) mol/L and L-NAME 10(-5) mol/L, the maximal response was decreased compared with that of the L-NAME group. Incubation with higher concentrations of L-Arginine did not change asthmatic rat tracheal responsiveness to Ach. Epithelium-denuded tracheal rings in the asthmatic rats showed a significant (P < 0.05) upward shift in the Ach concentration response curve; the maximal response was increased compared with the tracheal intact group. In the denuded tracheal rings, L-NAME and L-Arginine did not influence the shape of the Ach concentration-response curve and the maximal response. CONCLUSIONS: Endogenous nitric oxide, a mediator of bronchodilation, is synthesized from L-Arginine by NO synthase in asthmatic rats. The epithelium lining airway smooth muscle probably contributes to nitric oxide synthesis. Our finding suggests that the airway in asthmatic rats could not use exogenous L-Arginine to synthesize nitric oxide.