ENDOTHELIAL-CELL PHOSPHOLIPID DISTRIBUTION AND PHOSPHOLIPASE-ACTIVITYDURING ACUTE AND CHRONIC HYPOXIA

We have previously reported alterations in cyclooxygenase metabolism i n cultured aortic and pulmonary arterial endothelial cells exposed to acute and chronic hypoxia. These alterations depended on the duration and degree of the hypoxic exposure, on the vascular bed from which the endothelial cells were derived, and possibly on the availability of a rachidonic acid secondary to modifications in metabolic substrate, mem brane phospholipids, and/or membrane phospholipase activity. To invest igate this last point further, we have compared plasma membrane phosph olipid distribution and phospholipase activity in cultured aortic and pulmonary arterial endothelial cells exposed to both acute and chronic hypoxia, using two different precursors (acetic acid and arachidonic acid) and three different membrane preparations (cell homogenates, par tially purified plasma membranes, and highly purified plasma membranes ). We found that exposure to acute and chronic hypoxia has profound an d complicated effects on endothelial cell phospholipid composition and phospholipase activity and that these effects depend on the origin of the endothelial cells and the duration of hypoxia. Furthermore, we fo und that the alterations in endothelial cell phospholipid distribution in response to hypoxia depend on the purity of the plasma membrane pr eparation and the metabolic precursor used to study phospholipid metab olism. Finally, these studies suggested that alterations in phospholip ids during hypoxia occurred to a greater extent in compartments of end othelial cells other than the plasma membranes and that the well-recog nized tolerance of endothelial cells to hypoxia may be due, in part, t o preservation of the integrity of their plasma membranes during expos ure to acute and chronic hypoxia.