Effect of shear stress on 86Rb+ efflux from calf pulmonary artery endothelial cells

The effect of flow-induced shear stress on membrane K+ permeability was investigated by measuring 86Rb+ 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 in 86Rb+ 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 in 86Rb+ 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 in 86Rb+ 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 of 86Rb+ 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 of 86Rb+ 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.(ABSTRACT TRUNCATED AT 250 WORDS)