A transmural pressure gradient induces mechanical and biological adaptive responses in endothelial cells

Abstract

A sudden increase in the transmural pressure gradient across endothelial monolayers reduces hydraulic conductivity (Lp), a phenomenon known as the sealing effect. To further characterize this endothelial adaptive response, we measured bovine aortic endothelial cell (BAEC) permeability to albumin and 70-kDa dextran, Lp, and the solvent-drag reflection coefficients () during the sealing process. The diffusional permeability coefficients for albumin (1.33 Ϯ 0.18 ϫ 10 Ϫ6 cm/s) and dextran (0.60 Ϯ 0.16 ϫ 10 Ϫ6 cm/s) were measured before pressure application. The effective permeabilities (measured when solvent drag contributes to solute transport) of albumin and dextran (P e alb and P e dex ) were measured after the application of a 10 cmH2O pressure gradient; during the first 2 h of pressure application, P e alb , P e dex , and Lp were significantly reduced by 2.0 Ϯ 0.3-, 2.1 Ϯ 0.3-, and 3.7 Ϯ 0.3-fold, respectively. Immunostaining of the tight junction (TJ) protein zonula occludens-1 (ZO-1) was significantly increased at cell-cell contacts after the application of transmural pressure. Cytochalasin D treatment significantly elevated transport but did not inhibit the adaptive response, whereas colchicine treatment had no effect on diffusive permeability but inhibited the adaptive response. Neither cytoskeletal inhibitor altered despite significantly elevating both Lp and effective permeability. Our data suggest that BAECs actively adapt to elevated transmural pressure by mobilizing ZO-1 to intercellular junctions via microtubules. A mechanical (passive) component of the sealing effect appears to reduce the size of a small pore system that allows the transport of water but not dextran or albumin. Furthermore, the structures of the TJ determine transport rates but do not define the selectivity of the monolayer to solutes (). permeability; hydraulic conductivity; reflection coefficient; zonula occludens-1 THERE ARE TWO PRINCIPAL MECHANISMS of paracellular transport across the endothelium: bulk fluid movement or convection, a process driven by hydrostatic and oncotic pressure gradients, and diffusional exchange, a nonconvective process driven by concentration gradients (24, 42). These transport processes are characterized by three transport coefficients that define the barrier properties of the endothelium to water and solutes: hydraulic conductivity (L p ), diffusional permeability (P d ; i.e., when convection is zero), and the solvent-drag reflection coefficient (). The effective permeability (P e ; measured when solvent drag contributes to solute flux) is also reported frequently in the literature. It is conventional to regard the endothelial transport coefficients as constants; in other words, any observed change in transendothelial flux is attributed to changes in pressure and/or concentration gradients across the endothelium. However, it has become increasingly evident in recent years that endothelial transport coefficients also depend on the mechanical and hormonal environment of the cell layer.The endothelial cell...

Sexual dimorphism in the permeability response of coronary microvessels to adenosine

“…4. Of interest, the absolute values of are from 2 to 10 times lower than those reported in cultured cell models with continuous endothelium (8,9,12,18,61).…”

Transport in rat vessel walls. I. Hydraulic conductivities of the aorta, pulmonary artery, and inferior vena cava with intact and denuded endothelia

“…Recently, DeMaio et al (12) studied the sealing effect that transiently reduces the L p of bovine aortic endothelial cells cultured at zero pressure after a sudden rise in ⌬P. In the present study, we measured L p of vessels accustomed to and extracted under physiological pressure.…”

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.…”