Effect of altered flow on the pattern of permeability around rabbit aortic branches

Abstract

Uptake of circulating macromolecules by the aortic wall is greater downstream than upstream of branch sites in immature rabbits, but the opposite pattern is seen at later ages. The mature pattern is nitric oxide dependent; we tested whether it is also flow dependent. Intercostal arteries of anesthetized rabbits were occluded, sham operated, or left alone. Uptake of rhodamine-labeled albumin was assessed by quantitative fluorescence microscopy of the sections through the aorta. In mature animals, uptake was higher upstream than downstream of the control and sham-operated branches, but the pattern was reversed at occluded branches. In young animals, uptake was not significantly different between regions upstream and downstream of control, sham-operated, or occluded branches. The absence of the normal immature pattern may reflect an influence of anesthesia and will assist in the elucidation of mechanisms underlying this pattern. The data for mature animals provide the first direct evidence that flow determines permeability near arterial branches and may account for the inverse spatial correlation between shear stress and disease prevalence at branches of adult human arteries.

Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

“…The atheroprone areas such as the branch points, where blood flow is disturbed, have an increase in permeability to macromolecules, including 131 I-albumin (32) and Evans blue dyelabeled albumin in the pig (250) and rabbit (86, 97) aorta, and low-density lipoprotein (LDL) or fluorescent, radiolabeled and chromogenic tracer particles in normal or cholesterol-fed rabbit aorta (506, 507, 540, 542, 611). Many of these in vivo observations have been reproduced in in vitro studies.…”

Mass Transport in Arteries and the Localization of Atherosclerosis

“…In a subsequent study, an effect of blood flow pattern (and indirectly, fluid shear stress pattern) on albumin uptake around rabbit intercostal ostia was demonstrated by comparing the uptake pattern around normal ostia with the pattern around others that had the intercostal artery occluded to prevent flow into the side branch (128). In mature animals, the normal pattern of upstream predominance was converted to the immature downstream pattern around ostia that had been occluded for only 35 min.…”

“…Forster & Weinberg (125) shed light on the mechanism of this distribution pattern by observing that treatment of aortas with the NOS inhibitor L-NMMA for only 25 min could reverse the uptake pattern in mature animals to the juvenile pattern (reverting from upstream to downstream predominance of uptake). Because age, hypercholesterolemia, and inhibition of NOS all induce the upstream pattern, Staughton et al (128) have speculated that they all act via influences on NO synthesis.…”

Association of Coronary Wall Shear Stress With Atheromatous Plaque Vulnerability: A Systematic Review

“…In an experimental study on ApoE-/mice, in whom a cuff was placed around the carotid artery, regions located upstream of the cuff exhibited significant changes in ESS whereas segments located in the downstream area of the cuff exhibited changes in both ESS and direction [36]. Exposure of endothelial cells to low ESS lead to cell missalignement, allowing penetration by inflammatory mediators [37,38,39]. At the same time, mechanotransduction of ESS stimulated the release of bioactive mediators and micro-RNA synthesis [40].…”