Hindered barrier function has been implicated in the initiation and progres
sion of atherosclerosis, a disease of focal nature associated with altered
hemodynamics. In this study, endothelial permeability to macromolecules and
endothelial electrical resistance were investigated in vitro in monolayers
exposed to disturbed flow fields that model spatial variations in fluid sh
ear stress found at arterial bifurcations. After 5 h of flow, areas of high
shear stress gradients showed a 5.5-fold increase in transendothelial tran
sport of dextran (molecular weight 70,000) compared with no-flow controls.
Areas of undisturbed fully developed flow within the same monolayer, showed
a 2.9-fold increase. Monolayer electrical resistance decreased with exposu
re to flow. The resistance measured during flow and the rate of change in m
onolayer resistance after removal of flow were lowest in the vicinity of fl
ow reattachment (highest shear stress gradients). These results demonstrate
that endothelial barrier function and permeability to macromolecules are r
egulated by spatial variations in shear stress forces in vitro.