内皮素和一氧化氮平衡在哮喘犬发病机制中的作用

目的 探讨内皮素（ＥＴ）和一氧化氮（ＮＯ）平衡失调在支气管哮喘（简称哮喘）发病机制中的作用。方法 吸入猪蛔虫抗原复制过敏性哮喘犬模型，随机将实验动物分为五组，即对照组（Ａ组，６只），哮喘组（Ｂ组，６只）生理盐水＋哮喘组（Ｃ组，６只）Ｎ＾Ｇ－单甲基左旋精氨酸（Ｌ－ＮＭＭＡ）＋哮喘组（Ｄ组，６只）和左旋精氨本－ａｒｇ）＋哮喘组（Ｅ组，６只），观察了ＥＴ－１和ＮＯ对犬气道平滑肌的影响。结果 ＥＴ－１使呼

Effects of relative imbalance between endothlin-1 and nitric oxide on pathogenesis of the ascaris-induced asthma in dogs]

OBJECTIVE: To investigate the effects of relative imbalance between endothlin-1 (ET-1) and nitric oxide (NO) on pathogenesis of the ascaris-induced asthma in dogs. METHODS: Allergy induced asthma in dogs was established by inhaling ascaris antigen via an ultrasonic neblizer. At first, effects of ET-1 on respiratory system resistance (Rrs) and compliance (Crs) were studied in asthmatic dogs. Then, the roles of ET-1 and NO in regulating airway hyperresponsiveness (BHR) of asthma were investigated. Finally, effects of ET-1 on airway smooth muscle proliferating were observed. RESULTS: After intravenous injection of ET-1, there was a significant maximal increase in Rrs with (14.33 +/- 0.53) mm Hg.L-1.s-1 in normal dogs and (30.75 +/- 3.38) mm Hg.L-1.s-1 (P < 0.05) in asthmatic dogs. Also, there was a significant maximal decrease in Crs with (24.9 +/- 1.2) L/mm Hg in normal dogs and (14.8 +/- 0.9) L/mm Hg (P < 0.05) in asthmatic dogs. The dose-dependent bronchoconstriction in dogs was induced by three different doses of ET-1 (0.25, 0.5, 1.0 microgram/kg). ET-1 dose-response curve was significantly shifted upward by L-NMMA (P < 0.05). This effect was inhibited by L-arg (P < 0.05). Histological studies showed that ET-1 can stimulate airway smooth muscle proliferating and thickening after one week of ET-1 (4.0 micrograms/kg) i.v. administration. CONCLUSIONS: ET-1 might be involved in BHR that may be associated with immediate asthma response (IAR) in asthmatic dogs. ET-1 may be important for airway remodeling. The relative imbalance between ET-1 and NO may contribute to pathogenesis of asthma.