SHEAR-STRESS INCREASES HYDRAULIC CONDUCTIVITY OF CULTURED ENDOTHELIAL MONOLAYERS

To examine the effect of shear stress on hydraulic conductivity (L(p)) of bovine aortic endothelial cell monolayers grown on polycarbonate filters, we developed a rotating disk system, which imposed a defined shear stress while L(p) was measured. A 10-cmH(2)O pressure differential was applied to monolayers, and baseline L(p) was established between 1.65 +/- 0.85 and 4.94 +/- 1.05 x 10(-7) cm.s(-1).cmH(2)O(-1). One-hour exposure to 10 dyn/cm(2) shear stress caused a significant (P < 0.05) increase in L(p) by 2.16-fold (+/-0.42), and L(p) remained elevated when shear stress was removed. Three-hour exposure to shear stresses between 0.1 and 20.0 dyn/cm(2) revealed a threshold for shear-induced increase in L(p) of 0.5 dyn/cm(2). At 20 dyn/cm(2), L(p) initially decreased by 30% (+/-13.4%, P < 0.05) and then increased to a level 3.76-fold (+/-0.83, P < 0.05) greater than baseline L(p) at 3 h. The shear-induced increase in L(p) was reversed with dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 1 mM) and could be significantly (P < 0.05) inhibited when monolayers were preincubated with 0.3 mM DBcAMP, a concentration that did not significantly affect baseline L(p). Furthermore, preincubation with a general phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (1 mM), completely blocked the shear-induced increase in L(p). On the basis of these results, we conclude that shear stress alters endothelial L(p) through a cellular mechanism involving signal transduction, not by a purely physical mechanism.