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

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.