Mechanism of hypoxic injury to pulmonary artery endothelial cell plasma membranes.

We exposed monolayer cultures of pulmonary artery endothelial cells or plasma membranes derived from these cells to hypoxic (0 and 5% O2) and normoxic (20% O2; control) conditions and measured cellular contents of malondialdehyde and conjugated dienes, plasma membrane fluidity and lipid composition, and plasma membrane-dependent transport of 5-hydroxytryptamine (5-HT). Hypoxia caused significant increases in malondialdehyde and conjugated dienes, in fluidity, and in 5-HT transport. Hypoxia also caused a significant decrease in plasma membrane total phospholipids and a marked increase in plasma membrane free fatty acids that appeared to be due to release of fatty acids from the plasma membrane phospholipids. The increases in fluidity and 5-HT transport and the alterations in fatty acids were reversible after return to control conditions. These results indicate that hypoxia alters the physical state, lipid composition, and function of endothelial cell plasma membranes by a combination of stimulation of membrane lipid peroxidation and accelerated degradation of membrane phospholipids, the latter probably secondary to activation of membrane phospholipases.