The role of calcium ion in vasoreactivity in rat hypertensive pulmonary arteries during recovery from chronic hypoxia

为研究缺氧性肺动脉高压大鼠肺动脉L型钙通道依赖性舒张功能的变化及其在空气中恢复过程中的可逆性，将大鼠暴露于低压缺氧（380 mmHg）10 d，然后在空气中恢复3或14 d。在用PGF_（2α）预收缩的离体内皮完整的正常肺外动脉（EPA）和肺内动脉（IPAs）上，L型钙通道阻滞剂硝苯地平（10 ~（<-10>-10）μ <-5>M）呈浓度依赖性地引起舒张作用。与常氧大鼠相比，低氧大鼠EPA和IPA环的舒张作用在高浓度时显著增强。对硝苯地平的舒张反应在IPA中恢复3天后和在EPA中恢复14天后完全正常化。为了进一步研究增强的舒张，我们测试了对硝苯地平在内皮剥脱的PA环的反应。与肺动脉高压大鼠相比，高血压大鼠去内皮IPA和EPA对硝苯地平的舒张作用增强。恢复期高血压内皮完整和剥脱PA的恢复过程无差异。结果表明，这种增强的反应是由血管平滑肌细胞L型钙通道功能改变引起的。

To study the changes of L type calcium channel-dependent relaxation in structurally remodeled pulmonary arteries with hypoxic pulmonary hypertension and their reversibility during recovery in room air, rats were exposed to hypobaric hypoxia (air at 380 mmHg) for 10 days and then allowed to recover in room air for 3 or 14 days. In isolated endothelium-intact normal extra-pulmonary arteries (EPAs) and intrapulmonary arteries (IPAs), precontracted with PGF_<2α>, nifedipine (L type calcium channel blocker, 10^<-10>-10^<-5> M) caused relaxation in a concentration-dependent manner. The relaxation was markedly augmented in higher concentration in both EPA and IPA rings from hypoxic rats compared with those of normoxic rats. The relaxation response to nifedipine was normalized completely after 3 days recovery in IPA and 14 days in EPA. To further examine the augmented relaxation, we tested response to nifedipine in endothelium-denuded PA rings. The relaxation to nifedipine was augmented in both hypertensive endothelium-denuded IPA and EPAs compared with those of pulmonary hypertensive aretries. There was no difference in recovery process between hypertensive endothelium-intact and -denuded PAs during recovery period. These results suggested that this augmented response was caused by functional alteration associated with L type calcium channel in vascular smooth muscle cells.