Effect of pressure on hydraulic conductivity of endothelial monolayers: role of endothelial cleft shear stress

Effect of pressure On hydraulic conductivity of endothelial monolayers: Pol e of endothelial cleft shear stress. J. Appl. Physiol. 87(1). 261-268, 1999 . -Significant changes in transvascular pressure occur in pulmonary hyperte nsion, microgravity, and many other physiological and pathophysiological ci rcumstances. Using bovine aortic endothelial cells grown on porous, rigid s upports, we demonstrate that step changes in transmural pressure of 10, 20, and 30 cmH(2)O induce significant elevations in endothelial hydraulic cond uctivity (L-p) that require 5 h to reach new steady-state levels. The incre ases in L-p can be reversed by addition of a stable cAMP analog (dibutyryl cAMP), and the increases in L-p in response to pressure can be inhibited si gnificantly with nitric oxide synthase inhibitors (N-G-monomethyl-L-arginin e and nitro-L-arginine methyl ester). The increase in L-p was not due to pr essure-induced stretch because the endothelial cell (EC) support was rigid. It is unlikely that the increase in L-p was due to a direct effect of pres sure because exposure of the cells to elevated pressure (25 cmH(2)O) for 4 h had no effect on the volume flux driven by a transmural pressure of 10 cm H(2)O. We hypothesize that elevated endothelial cleft shear stress induced by elevated transmural flow in response to elevated pressure stimulates the increase in L-p, through a nitric oxide-cAMP-dependent mechanism. This is consistent with recent studies of the effects of shear stress on the lumina l surface of ECs, We provide simple estimates of endothelial cleft shear st ress, which suggest magnitudes comparable to those imposed by blood flow on the luminal surface of ECs.