Effect of shear stress on⁸⁶Rb⁺ efflux from calf pulmonary artery endothelial cells

The effect of flow-induced shear stress on membrane K⁺ permeability was investigated by measuring⁸⁶Rb⁺ efflux in cultured calf pulmonary artery endothelial cells. Cells were subjected to step changes in shear stress from 1 dyn/cm² to 2.4, 4.8, or 10 dyn/cm² in a parallel-plate flow chamber. Increasing shear stress produced a graded, transient increase in⁸⁶Rb⁺ efflux which peaked within 1 min and subsequently declined rapidly toward pre-stimulus levels. Upon returning shear stress to 1 dyn/cm²,⁸⁶Rb⁺ efflux initially decreased, but returned slowly to basal values. In contrast, application of bradykinin at a constant shear stress of 1 dyn/cm² produced a transient increase in⁸⁶Rb⁺ efflux that was followed by a sustained elevated phase during which time efflux gradually returned to pre-stimulus levels. In order to exclude the possibility that the transient increase in⁸⁶Rb⁺ efflux with shear stress simply reflects a flow-dependent change in the washout of radiotracer, the transient convection-diffusion equation was solved using finite element simulation. When the flux of⁸⁶Rb⁺ from the cell monolayer was assumed to be constant with time, the mathematical model predicted an increase in efflux rate coefficients upon step increases in flow that were only 7-19% of that observed experimentally. The numerical predictions correlated well with the experimentally obtained peaks when the flux of⁸⁶Rb⁺ from the cell monolayer was simultaneously increased with flow to a new steady value. These simulations however, could not predict the transient nature of the response to increased shear stress. The results from the computer modeling suggest that the transient increase in⁸⁶Rb⁺ efflux does not reflect a washout phenomenon and supports the hypothesis that shear stress produces a graded, transient increase in the K⁺ permeability of vascular endothelial cells.