Influence of ischemia and reperfusion on plasma endothelin -1 and endothelin -1 binding sites in pulmonary vasculature.

内皮素是一种由血管内皮细胞产生的强效血管活性多肽，在肺循环调节中发挥重要作用。为探讨内皮素及其结合部位在兔肺缺血再灌注损伤或肺组织病理生理反应中的作用，我们测定了兔肺缺血(30分钟)和再灌流(60分钟)后血浆内皮素-1(ET-1)、硝酸盐和亚硝酸盐(NOx)的浓度以及肺功能(平均肺动脉压、最大肺内压和出血氧分压)。用体外放射自显影技术研究了肺组织中内皮素-1的结合。最后，我们评价了ET-A和ET-B非选择性内皮素受体拮抗剂TAK-044对肺缺血再灌注损伤的影响。每2个…再灌流0min后，对照组平均肺动脉压分别为29.3±2.8、28.7±2.2、28.9±4.6，缺血组分别为54.0±4.4、52.7±5.6、53.5±4.9，最大肺内压分别为11.6±0.9、11.1±0.9。流出血氧分压对照组分别为649.5±13.2、650.2±26.3、614.2±26.3，缺血组分别为588.1±9.2、497.6±48.9、356.8±50.3。再灌流60min后，血浆NOx含量明显低于对照组(p<0.01)，再灌流60min后，肺组织ET-B结合密度明显低于对照组(p&lt；0.05)。TAK-044组在缺血前给予TAK-044(5 mg/kg)，再灌流期间每20min给药一次，平均肺动脉压分别为32.2±3.0、35.0±1.4、37.2±1.2；肺内压峰值分别为12.0±0.5、12.2±0.5、12.8±0.4，流出血氧分压分别为557.2±15.9、551.1±11.2、535.2±15.8。非选择性ET-A和ET-B受体拮抗剂Tak-044对肺缺血再灌注损伤有保护作用。较少

Endothelin is a potent vasoactive peptide produced by vascular endothelial cells and is believed to play an important role in regulation of pulmonary circulation. Various pathologic conditions with pulmonary hypertension have been found to be associated with elevated levels of plasma endothelin-1.To invesitgate the role of endothelin and endothelin binding sites on the pathophysiological response to ischemia-reperfusion injury or lung, we measured a concentration of plasma endothelin-1, NOx (nitrate and nitrite) and pulmonary function (mean pulmonary artery pressure, peak intrapulmonary pressure and oxygen tension of effluent blood) in isolated blood-perfused rabbit lung after ischemia (30 minutes) and reperfusion (60 minutes). l125-labeled endothelin-1 binding of lung tissue was studied using an in vitro autoradiographic technique. Finally, we evaluated the effects of an ET A and ET B non-selective endothelin receptor antagonist, TAK-044, on ischemia-reperfusion injury of lung.Every 2 … More 0 minutes during reperfusion, mean pulmonary artery pressure (mmHg) was 29.3 ± 2.8, 28.7 ± 2.2, 28.9 ± 4.6 in control group (reperfused immediately after hervesting) and 54.0 ± 4.4, 52.7 ± 5.6, 53.5 ± 4.9 in ischemic group (reperfused after 30 minutes ischemia), respectively ; peak intrapulmonary pressure (mmHg) was 11.6 ± 0.9, 11.1 ± 0.9. 11.9 ± 1.1 in control group and 15.5 ± 0.9, 17.5 ± 0.8, 20.3 ± 1.7 in ischemic group, respectively ; oxygen tension of effluent blood (mmHg) was 649.5 ± 13.2, 650.2 ± 26.3, 614.2 ± 26.3 in control group and 588.1 ± 9.2, 497.6 ± 48.9, 356.8 ± 50.3 in ischemic group, respectively.In ischemic group, plasma endothelin-1 was greater (p<0.01) and plasma NOx was lower (p<0.05) than that of control group after 60 minutes reperfusion, the density of ET B binding was decreased in pulmonary artery compared with control group (p<0.05) after 60 minutes reperfusion.In TAK-044 group, TAK-044 (5mg/kg) was adninistered just before ischemia ; every 20 minutes during reperfusion, mean pulmonary artery pressure (mmHg) was 32.2 ± 3.0, 35.0 ±± 1.4, 37.2 ± 1.2, respectively ; peak intrapulmonary pressure (mmHg) was 12.0 ± 0.5, 12.2 ± 0.5, 12.8 ± 0.4, respectively ; oxygen tension of effluent blood (mmHg) was 557.2 ± 15.9, 551.1 ± 11.2, 535.2 ± 15.8, respectively.These results suggest that the increase of plasma endothelin-1, the decrease of plasma NOx and the deminution of ET B binding sites in pulmonary artery play an important role in ischemia-reperfusion injury of lung. TAK-044, an ET A and ET B non-selective endothelin receptor antagonist, has a beneficial effect in protecting the lung from ischemia-reperfusion injury. Less