Role of shear and leukocyte adherence on venular permeability in the rat mesentery

The role of fluid shear stress on permeability has been controversial. In vitro studies have shown higher endothelial permeability with an increase in shear, but in vivo higher shear can also decrease permeability by attenuating leukocyte adherence (e.g., during an inflammatory response). The potential contribution of fluid shear and leukocyte adherence acting simultaneously to determine basal levels of permeability remains unresolved. Therefore, the purpose of this study was to understand the effects of basal shear and leukocyte adherence on venular permeability of the rat mesentery. Using a modification of current measurement techniques, we were able to quantify permeability under physiological flow and estimate its convective and diffusive components. We found that water filtration plays a minor role in the transport of albumin across venular endothelium, that permeability exhibits a moderately linear correlation with shear, and that the number of leukocytes adherent to the endothelium accounts for the majority of the scatter in this correlation. Multiple regression analysis of permeability as a function of shear rate and leukocyte adherence revealed significant roles for both factors (regression P < 0.01, r2 = 73.9%).