Nonsteady pressure affects large arteries and endothelium

Abstract

Convective fluid motion through artery walls aids in transvascular transport of macromolecules. Although measurements of convective filtration have been reported, they were all obtained under constant transmural pressure. However, arterial pressure in vivo is pulsatile. Therefore experiments were designed to compare filtration under steady and pulsatile pressure conditions. Hydraulic conductance was measured in cannulated excised rabbit carotid arteries at steady pressure. Next, pulsatile pressure trains were applied within the same vessels, and simultaneously, arterial distension was monitored using Optical Coherence Tomography (OCT). For each pulse train, the volume of fluid lost through filtration was measured (subtracting volume change due to residual distension), and compared to that predicted from steady pressure measurements. In order to determine the role of the endothelium in this response, and the effect of increasing pulsatile frequency from an initial value, one of each pair was de-endothelialized in some cases, and in other experiments a pulsatile pressure of 1 Hz was initially applied, followed by a pulsatile frequency of 2 Hz. In all cases the experimental filtration volumes were significantly increased compared to those predicted for steady pressure, but over time, the magnitude of the excess fluid loss was reduced. For de-endothelialized vessels, this reduction was not so marked. These studies suggest that changes in arterial pulsatility may transiently increase convective flux of macromolecules into the artery wall and that this is regulated by the endothelium. In a parallel study, Bovine Aortic Endothelial Cells (BAEC) were exposed to a transient pressure gradient and then held at 20 mmHg for ten or thirty minutes. After staining for actin fibers and/or catenin, the cells were examined using a deconvolution microscope. The location of actin fibers changed from the body of the cell (central fibers) to the edges of the cell (peripheral fibers), and beta-catenin increased around the periphery. This result indicates that cultured endothelial cells can sense a change in transcellular pressures and respond so as to maintain cell-to-cell adhesion. Overall, the observed responses of arteries and endothelial cells to transient pressure gradients in these studies suggest a dynamic role for the endothelium in regulating transvascular transport in vivo.