Effects of endothelial denudation and cholesterol feeding on in vivo transport of albumin, glucose, and water across rabbit carotid artery.

Abstract

An in vivo system for studying arterial transport was developed which utilized the rabbit carotid artery perfused in vivo with Dulbecco's modified Eagle's medium containing 125I-labeled albumin, [3H]-3-methyl-d-glucose, or tritiated water. The appearance of labeled materials in jugular venous blood was measured serially over 4 hours. Vascular integrity was assessed by scanning electron and transmission microscopy. Maintenance of endothelial integrity appeared dependent on perfusion with nutrient tissue culture medium, use of papaverine to inhibit arterial spasm, and circulation of the medium under pressure. Acute endothelial denudation with a balloon catheter induced an approximate 10-fold increase in plasma concentration of labeled albumin and a 3-fold rise in plasma [3H]-3-methyl-d-glucose activity, compared with results in animals with intact endothelium. Increased appearance of tritiated water in venous blood was also observed in the rabbits with denuded endothelium, although the relative rise was less than that with albumin or glucose. Feeding rabbits a diet containing 1.5% cholesterol for periods of 16-28 weeks produced approximately 10-fold increases in plasma concentration of 125I-labeled albumin after arterial perfusion to levels comparable to those present in chow-fed rabbits with experimental endothelial denudation. The increases in albumin transport with cholesterol feeding occurred even though a relatively small fraction of the intimal surface was involved with lesions. The results suggest that the arterial endothelium provides a relative barrier to albumin and, to a lesser extent, glucose and water. The findings also suggest that cholesterol feeding markedly increases arterial permeability to albumin, to a degree that is disproportionately greater than the extent of atherosclerotic involvement of the intimal surface.