Transport in rat vessel walls. II. Macromolecular leakage and focal spot size growth in rat arteries and veins

Abstract

Transendothelial lipid transport into and spread in the subendothelial intima of large arteries, and subsequent lipid accumulation, appear to start plaque formation. We experimentally examine transendothelial horseradish peroxidase (HRP) transport in vessels that are usually, e.g., pulmonary artery (PA), or almost always, e.g., inferior vena cava (IVC), atherosclerosis resistant vs. disease prone, e.g., aorta, vessels. In these vessels, HRP traverses the endothelium at isolated, focal spots, rather than uniformly, for short circulation times. For femoral vein HRP introduction, PA spots have 30-s radii [ approximately 53.2 microm (SD 10.4); compare aorta: 54.6 microm (SD 8.75)] and grow quickly from 30 s to 1 min (40%, P<0.05) and more slowly afterward (P>0.05). This trend resembles the aorta, suggesting the PA has a similarly sparse intima. With carotid artery (CA) HRP introduction, the 30-s spot (132.86 +/- 37.32 microm) is far larger than the PAs, grows little ( approximately 28%, P<0.05) from 30 to 60 s, and is much flatter than the artery curves. Transverse electron microscopic sections after approximately 10 min HRP circulation show thin, intense staining immediately beneath both vessels' endothelia with an almost step change to diffuse staining beyond. This indicates the existence of a sparse, subendothelial intima, even when there is no internal elastic lamina (IVC). This motivates a simple model that translates growth rates into lower bounds for the flow through focal leaks. The model results and our earlier wall and medial hydraulic conductivity data explain these spot growth curves and point to differences in transport patterns that might be relevant in understanding the immunity of IVC to disease initiation.

A theory for water and macromolecular transport in the pulmonary artery wall with a detailed comparison to the aorta

“…1 Since electron micrographs (45,46) show the PA and aorta have the same basic structural layers: endothelium, SI, IEL, media, and adventitia, Fig. 1, A and B, applies to both vessels the same basic 2-D convection-diffusion model (similar, but not identical, to that in Refs.…”

“…Chuang et al (9) and Shou et al (46) both observed this rapid HRP spot growth en face in rat aorta. HRP spots grow extremely rapidly in the first minute after HRP injection and more slowly thereafter.…”

“…They found the fractional albumin volume much greater in the PA than in the aorta wall. Shou et al (46) showed that, at physiological lumen pressures ⌬P*, the rat PA wall has a much higher hydraulic conductivity L p * than its aortic wall, both with intact and denuded endothelium. Their data indicate similar endothelial L p * (computed at the lowest ⌬P*).…”

“…Despite the PA slower radial SI tracer advection, Shou et al (46) found that both have remarkably identical HRP spot growths, further suggesting the above fitting procedure is missing something important. All of these calculations compare spots with SI HRP spread, presuming media HRP is negligible.…”

“…One measures spot radii by taking light micrographs en face from above a vessel lit from below. This view through the off-white, adventitia-free vessel (9,46) Let A() be the HRP reaction product's absorbance, the logarithm of the ratio I/I 0 of the intensities of the transmitted and incident beams, at the interrogating wavelength , ε() the HRP absorptivity, z the light path normal to the endothelium, L ϭ L 1 ϩ L 2 , and C(r, z) the nondimensional absorber (tracer) concentration. Beer-Lambert's Law of optics states…”