埃他卡林对低氧暴露大鼠脑和肺微动脉选择性扩张作用

目的:研究低氧暴露对大鼠脑和肺微动脉内皮功能的影响以及埃他卡林(Ipt)对以上微动脉的扩张作用特征。方法:将雄性SD大鼠随机分为2组,常压常氧组(control)和低氧暴露组(hypoxic),后者置于常压低氧暴露舱内(O27.8%)8 h。分离大鼠管径为(204±5)μm的脑基底动脉、肺微动脉组织,利用DMT微血管张力测定仪在6nmol/L内皮素-1(ET-1)致血管预收缩条件下,利用乙酰胆碱(ACh)考察微动脉内皮功能及观察不同浓度Ipt对脑和肺微动脉张力变化的影响。结果:与常压常氧组对比,10-5 mol/L乙酰胆碱(ACh)对低氧暴露脑肺微动脉扩张率显著降低(P0.05);新型ATP敏感性钾通道开放剂Ipt在(10-11~10-3)mol/L对低氧暴露肺微动脉呈剂量依赖性扩张作用,明显强于对常压常氧组(P0.01),在(10-11~10-3)mol/L对低氧暴露脑微动脉呈剂量依赖性扩张作用,但与常压常氧组相比无显著差异。结论:低氧暴露可导致脑基底动脉和肺微动脉内皮功能受损,Ipt具有选择性增强扩张低氧暴露肺微动脉的作用,但不影响以上条件低氧暴露后脑基底动脉的扩张作用,提示该药可应用于改善低氧暴露所致的肺微血管收缩,为Ipt发展为新型治疗肺动脉高压的药物提供理论基础。

The selective dilatation effects of iptakalim on basilar and pulmonary arterioles in high-altitude hypoxic rats

Objective： To study the selective dilatation effects of iptakalim （Ipt） on basilar and pulmonary arterioles, and endothelial cell function of these arterioles in hypoxic rats. Methods： SD male rats were divided into 2 groups： control and hypoxic group fed in normobaric hy- poxic environment （O2 7.8%, 8 h）. Arteriole rings about （204 ＋ 5） tan were isolated and the tension of hypoxic arterioles pre-contracted by 6nmol/L endothelin-l（ET-1） was observed with wire myograph system model （DMT 610 m）. The relaxing response of hypoxic arterioles in- duced by different concentration of Ipt were detected and endothelial activity was also tested by acetylcholine. Results： 10.5 mol/L acetyl- choline （ACh）-mediated vasodilatation of basilar and pulmonary arterioles was ~eatly reduced in the hypoxic group than those in control group （ P 〈 0.05）. Compared with normal group, a novel ATP-sensitive potassium ehaunel opener Ipt at the concentration ranging from 10-11 mol/L to 10-3 mol/L, caused stronger dose dependent vasodilatation on hypoxie pulmonary arterioles, and there was no significant difference between control and hypoxic basilar arterioles. Conclusion： The endothelial function of basilar and pulmonary arterioles was damaged under hypoxic state, and Ipt selectively increased dilatation effects on hypoxic pulmonary arterioles, but not on hypoxic basilar arterioles which could improve high altitude pulmonary edema pathological state and be the novel drug in the treatment of pulmonary hypertension.