HYPOXIA AND REOXYGENATION STIMULATE BIPHASIC CHANGES IN ENDOTHELIAL MONOLAYER PERMEABILITY

Incubation of bovine pulmonary microvascular endothelial (BPMVE) cells in low O-2 content (95% N-2-5% CO2) for 4 h increased monolayer perme ability to dextran almost twofold and also increased the incidence of intercellular gaps and intracellular actin stress fibers. Hypoxic incu bation decreased the extracellular matrix contents of fibronectin and vitronectin, proteins that serve as anchorage points for the endotheli al cells. This state was reversed after 24 h of hypoxic incubation, an d the BPMVE monolayer permeability to dextran was less than that of no rmoxic controls. The monolayer had fewer intercellular gaps and stress fibers, and the extracellular matrix contained increased amounts of f ibronectin, vitronectin, and type I collagen. These alterations stimul ated by 24 h of hypoxic incubation were resolved within 4 h of reoxyge nation in room air supplemented with 5% CO2. These studies indicate th at incubation of endothelial monolayers in hypoxic conditions first in creases and then decreases monolayer permeability, through increased a nd decreased formation of intercellular gaps.