慢性缺氧对肺动脉内皮依赖性和非内皮依赖性舒张反应的影响

CHRONIC HYPOXIA INHIBITS ENDOTHELIUM-DEPENDENT AND ENDOTHELIUM-INDEPENDENT RELAXATION OF PULMONARY ARTERIAL RINGS

本实验用生物测定法观察了模拟海拔5000m高度连续缺氧20d对大鼠肺动脉内皮依赖性和非内皮依赖性舒张反应的影响。结果显示慢性缺氧明显抑制了肺内和肺外动脉对乙酰胆碱、ATP、硝普钠和异丙肾上腺素舒张反应的敏感性和反应性。在浓度为10^(-6)mol/L时,缺氧组大鼠肺内动脉对乙酰胆碱、硝普钠和异丙肾上腺素的舒张反应分别只有对照组大鼠的61.3％、75.9％和61.7％,对浓度为1.8×10^(-5)mol/L的ATP的舒张反应只有对照组大鼠的64.9％。研究表明,ATP和乙酰胆碱主要是通过内皮舒张因子使肺动脉产生内皮依赖性舒张反应,硝普钠和异丙肾上腺素分别通过直接激活血管平滑肌细胞鸟苷酸环化酶和β受体使血管产生非内皮依赖性舒张反应。缺氧同时抑制了肺动脉内皮依赖性和非内皮依赖性舒张反应,提示慢性缺氧可能抑制了正常肺内舒血管活性物质的生理作用。

The mechanism of hypoxic pulmonary hypertension remains unclear. This study was designed to investigate whether endothelium-dependent or endothelium-independent relaxation of pulmonary artery might be depressed by chronic hypoxia. Male Wistar rats were kept in hypobaric chamber (simulated altitude 5 000 m.) for 20 days. The rings of extra-pulmonary artery (EPPA) or intrapulmonary artery (IPPA) were suspended in an organ bath containing oxygenated Krebs's solution at 37℃. The results showed that chronic hypoxia significantly depressed not only endothelium-dependent relaxation elicited by acetylcho-line and ATP, but also endothelium-independent relaxation elicited by sodium nitroprusside and isoproterenol in the rings of both EPPA and IPPA. Our results suggest that chronic hypoxia blocks physiological effects of vasodilators in the lung.