Farber H W, Barnett H F
Pulmonary Center, Boston University School of Medicine, Mass. 02118.
Circ Res. 1991 May;68(5):1446-57. doi: 10.1161/01.res.68.5.1446.
In vivo, a marked difference in blood oxygen tension exists between the pulmonary artery and the aorta. Responses of vascular endothelial cells from these vessels to changes in ambient oxygen might be influenced by the oxygen tension to which they are continuously exposed in vivo or by their anatomic site. To explore this hypothesis, we initially studied the production of the cyclooxygenase metabolites prostacyclin and thromboxane in bovine aortic and main pulmonary arterial endothelial cells grown in 21% O2 and exposed to different degrees of acute hypoxia over a wide range of times. We found that short-term hypoxia (3% or 0% O2) rapidly and transiently activates the cyclooxygenase pathway in both cell types, with a more rapid response in bovine aortic endothelial cells. To determine whether culture in an oxygen tension similar to that to which main pulmonary arterial endothelial cells are exposed in vivo alters this response, we evaluated these cyclooxygenase metabolites in bovine aortic and main pulmonary arterial endothelial cells cultured long-term in 3% O2, both at baseline and after exposure to acute anoxia (0% O2). In both cell types, we found a decrease in prostacyclin and thromboxane synthesis at baseline and evidence of an increase in the Vmax of thromboxane synthetase following stimulation with exogenous arachidonic acid. In chronically hypoxic cells exposed to acute anoxia, there were marked differences in enzyme activity compared with that in endothelial cells maintained in 21% O2 with differences depending on the origin of the endothelial cells. In bovine aortic endothelial cells, production of neither cyclooxygenase metabolite increased; in bovine main pulmonary arterial endothelial cells, only thromboxane production increased, suggesting isolated activation of the cyclooxygenase-thromboxane synthetase pathway. These studies demonstrate that acute and chronic hypoxia have profound effects on endothelial cell cyclooxygenase metabolism and that these effects depend on the duration and degree of the hypoxic exposure and the vascular bed from which the endothelial cells are derived.
在体内，肺动脉和主动脉之间的血氧张力存在显著差异。这些血管的血管内皮细胞对环境氧变化的反应可能受到它们在体内持续暴露的氧张力或其解剖位置的影响。为了探究这一假设，我们首先研究了在21%氧气环境中生长并在广泛的时间段内暴露于不同程度急性缺氧的牛主动脉和主肺动脉内皮细胞中环氧化酶代谢产物前列环素和血栓素的产生。我们发现短期缺氧（3%或0%氧气）能迅速且短暂地激活两种细胞类型中的环氧化酶途径，牛主动脉内皮细胞的反应更为迅速。为了确定在与主肺动脉内皮细胞在体内所暴露的氧张力相似的环境中培养是否会改变这种反应，我们评估了在3%氧气环境中长期培养的牛主动脉和主肺动脉内皮细胞在基线时以及暴露于急性缺氧（0%氧气）后的这些环氧化酶代谢产物。在两种细胞类型中，我们发现基线时前列环素和血栓素合成减少，并且在外源性花生四烯酸刺激后血栓素合成酶的Vmax有增加的迹象。在暴露于急性缺氧的慢性缺氧细胞中，与维持在21%氧气环境中的内皮细胞相比，酶活性存在显著差异，差异取决于内皮细胞的来源。在牛主动脉内皮细胞中，两种环氧化酶代谢产物的产生均未增加；在牛主肺动脉内皮细胞中，只有血栓素的产生增加，表明环氧化酶 - 血栓素合成酶途径被单独激活。这些研究表明，急性和慢性缺氧对内皮细胞环氧化酶代谢有深远影响，并且这些影响取决于缺氧暴露的持续时间和程度以及内皮细胞所源自的血管床。
