The role of fluid shear stress on permeability has been controversial. in v
itro studies have shown higher endothelial permeability with an increase in
shear, but in vivo higher shear can also decrease permeability by attenuat
ing leukocyte adherence (e.g., during an inflammatory response). The potent
ial contribution of fluid shear and leukocyte adherence acting simultaneous
ly 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 pe
rmeability under physiological flow and estimate its convective and diffusi
ve components. We found that water filtration plays a minor role in the tra
nsport 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 th
is correlation. Multiple regression analysis of permeability as a function
of shear rate and leukocyte adherence revealed significant roles for both f
actors (regression P < 0.01, r(2) = 73.9%). (C) 2001 Academic Press.