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

Abstract

Significant changes in transvascular pressure occur in pulmonary hypertension, microgravity, and many other physiological and pathophysiological circumstances. Using bovine aortic endothelial cells grown on porous, rigid supports, we demonstrate that step changes in transmural pressure of 10, 20, and 30 cmH(2)O induce significant elevations in endothelial hydraulic conductivity (L(p)) that require 5 h to reach new steady-state levels. The increases 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 significantly with nitric oxide synthase inhibitors (N(G)-monomethyl-L-arginine and nitro-L-arginine methyl ester). The increase in L(p) was not due to pressure-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 pressure 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 cmH(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 luminal surface of ECs. We provide simple estimates of endothelial cleft shear stress, which suggest magnitudes comparable to those imposed by blood flow on the luminal surface of ECs.

Regulation of capillary hydraulic conductivity in response to an acute change in shear

“…ϩP Ͻ 0.05, significantly different from 1. of the feed vessel. Therefore, a question is whether elevated pressure could cause a "sealing effect" that has been described for endothelial monolayers in vitro (7,38,39). Turner (39) observed a decrease in the rate of liquid flow per unit area with time under exposure of constant pressure in monolayers of arterial endothelium.…”

“…For example, when a capillary is occluded at its downstream end, pressure throughout the vessel increases to that of the feeding arteriole. Recent studies (7,38) indicate that a step increase in hydrostatic pressure causes a decrease in L p in what has been called a "sealing effect." However, the time courses of the changes in L p in these studies were over a period of minutes to hours.…”

Transendothelial flow inhibits neutrophil transmigration through a nitric oxide-dependent mechanism: potential role for cleft shear stress

“…Increased transendothelial flow occurs in a variety of pathophysiological conditions. Sustained step increases in transendothelial pressure are associated with increased endothelial hydraulic conductivity (L p ) in vitro (9,30) and in vivo (12). The associated increase in L p is thought to involve a nitric oxide-dependent mechanism (9,30).…”

“…Sustained step increases in transendothelial pressure are associated with increased endothelial hydraulic conductivity (L p ) in vitro (9,30) and in vivo (12). The associated increase in L p is thought to involve a nitric oxide-dependent mechanism (9,30). Nitric oxide (NO), synthesized in vascular endothelial cells by endothelial NO synthase (eNOS), reportedly inhibits neutrophil binding to endothelial cells and suppresses transendothelial migration.…”

Biofluid Flow and Heat Transfer

“…However, the contribution of the transcellular transfer to the net flux is usually supposed to be either small or negligible. In addition, elevated transmural pressures on endothelial cell culture on rigid, porous supports increase the endothelial hydraulic conductivity [76]. It is postulated that elevated shear stresses in endothelial clefts caused by increased transmural flow heightens the hydraulic conductivity.…”