目的:考察缺氧及皮下注射野百合碱诱导肺动脉高压模型大鼠肺动脉和尾动脉血管活性变化及药物CPU0213和CPU86017的体外急性给药疗效。方法:建立缺氧及皮下注射野百合碱所致大鼠肺动脉高压模型。造模5周后,大鼠乌拉坦麻醉,经右颈静脉插管,进行血流动力学实验,记录中心静脉压、右心室收缩压等血流动力学指标。随后,处死大鼠,分离肺内动脉和尾部腹侧动脉,进行离体血管环实验,观察分别由乙酰胆碱和苯肾上腺素所致大鼠肺动脉和尾动脉血管舒缩活性的变化以及经CPU0213和CPU86017温孵对病损血管的离体治疗作用。结果:慢性缺氧可致大鼠肺动脉及尾动脉血管收缩增强,而野百合碱致血管收缩削弱。慢性缺氧和注射野百合碱均可致大鼠肺动脉和尾动脉血管舒张削弱。CPU0213和CPU86017温孵能不同程度地改善两种模型大鼠的血管收缩和内皮依赖性舒张功能,CPU0213能部分恢复而CPU86017却进一步削弱两种模型大鼠中KATP介导的血管舒张活性。结论:慢性缺氧和注射野百合碱均损伤血管活性,同时造成尾动脉KATP功能障碍,且慢性缺氧对肺动脉损伤的选择性高于野百合碱。CPU0213体外急性给药对血管活性有较好的改善作用,而CPU86017可部分改善血管活性,但对KATP有阻断作用。
Objective: To investigate the changes of vasomotor of pulmonary and tail arteries from two pulmonary hypertension rat models induced by hypoxia and monocrotaline (MCT) respectively and in vitro intervention of CPU0213 and CPU86017. Methods: Two pulmonary hypertension rat models were respectively established by hypoxia or MCT (ip). 5 weeks after modeling, all rats were anesthetized with urethane, followed by intubating rat right jugular veins and a hemodynamic test was conducted, measuring hemodynamic parameters, such as CVP, RVSP, RV ± dp/dtmax and so on. Then the rats were killed and their pulmonary and tail artery vessels were isolated and incubated in K-H solution, where the changes of the vasomotor ofpulmonary and tail artery vessels induced by Ach and Phe as well as the therapeutic effect of CPU86017 or CPU0213 in vitro were observed. Results: Both chronic hypoxia and MCT caused the inhibition of vasorelaxation in artery. MCT also inhibited contractive function of the artery vessels while chronic hypoxia enhanced it inordinately. The vasomotors of the artery vessels from two models were improved to different degree after incubation with CPU86017 or CPU0213. CPU0213 restored partly but CPU86017 reduced further KATp-mediated vasorelaxation. Condusion: Both chronic hypoxia and MCT could damage vasomotor and result in KATP dysfunction of tail artery. Chronic hypoxia damages selectively pulmonary artery higher than MCT. Acute treatment of CPU0213 in vitro can give good improvement to vasomotor while CPU86017 may partly improve vasomotor but block the KATP,.