Dual effect of fluid shear stress on volume-regulated anion current in bovine aortic endothelial cells.

The key mechanism responsible for maintaining cell volume homeostasis is activation of volume-regulated anion current (VRAC). The role of hemodynamic shear stress in the regulation of VRAC in bovine aortic endothelial cells was investigated. We showed that acute changes in shear stress have a biphasic effect on the development of VRAC. A shear stress step from a background flow (0.1 dyn/cm(2)) to 1 dyn/cm(2) enhanced VRAC activation induced by an osmotic challenge. Flow alone, in the absence of osmotic stress, did not induce VRAC activation. Increasing the shear stress to 3 dyn/cm(2), however, resulted in only a transient increase of VRAC activity followed by an inhibitory phase during which VRAC was gradually suppressed. When shear stress was increased further (5-10 dyn/cm(2)), the current was immediately strongly suppressed. Suppression of VRAC was observed both in cells challenged osmotically and in cells that developed spontaneous VRAC under isotonic conditions. Our findings suggest that shear stress is an important factor in regulating the ability of vascular endothelial cells to maintain volume homeostasis.