The effect of blood pressure on the passage of labeled plasma albumin into canine aortic wall.

According to one of the common theories (1, 2) of the genesis of atherosclerosis, that disease arises as a complication of the passage of plasma water and its solutes through arterial tissue. In this passage the plasma constituents are believed to move from the arterial lumen across the intimal endothelium and on through the arterial tissue. The low density lipoproteins are thought to share in this general movement of plasma constituents through arterial wall but to have characteristics that lead to their being trapped in the arterial intima where they decompose, leaving lipid deposits that eventually form atheromata. Because of this, it appears likely that information about the movement through arterial wall of plasma proteins, and especially of plasma lipoproteins, may increase our understanding of the genesis of atherosclerosis. Studies of the movement of the lipoproteins into arterial wall have proved difficult to perform and interpret (3) because the lipoproteins contain both lipid and protein moieties and because their lipid components exchange freely between the various lipoproteins (4) and with the lipids of cells (5). It therefore seemed advantageous to develop information about the passage of a simple plasma protein like albumin through arterial wall because such studies are relatively easy to interpret and can be carried out relatively rapidly to form a background for the more involved study of the passage of lipoproteins into arterial tissue. Our studies suggest that such a background will be pertinent. This conclusion is based on the similarities between the entrance rates of albumin into canine aortic wall, the entrance of labeled cholesterol into canine aortic wall, and the accumulation of cholesterol in canine aortic wall in experimental atherosclerosis. Albumin enters the inner layer of the aortic wall with a gradient of rates (6). The rate of entrance is fastest in the proximal aorta and becomes progressively less rapid down the length of the aorta. Labeled plasma cholesterol enters the aortic wall with a similar rate gradient (7). This similarity suggests that the plasma lipoproteins of the normal dog also enter aortic wall with a gradient of rates, but the lability of cholesterol as a label for lipoproteins renders such a conclusion tentative. Early in the development of experimental canine atherosclerosis the accumulation of cholesterol in the inner layer of the aortic wall forms a gradient (8) similar to the gradient of the entrance rate of albumin. This suggests that some common factor is involved in the entrance of albumin and the accumulation of cholesterol, and is compatible with the hypothesis that low density lipoproteins enter aortic wall with a gradient of rates and thus give rise to the observed gradient of cholesterol concentrations. Alternative explanations are of course possible. In addition, the fact that later in the course of experimental canine atherosclerosis the gradient disappears and the concentration of cholesterol comes to be highest in the abdominal aorta makes the interpretation of the later course of the disease highly speculative. Despite the foregoing qualifications, the observed similarities of the entrance rate of labeled albumin in normal dogs, the entrance rate of labeled cholesterol in normal dogs, and the rate of accumulation of cholesterol in dogs on an atherogenic regimen do suggest that information about the movement of albumin through arterial wall will provide a pertinent background to the study of the movement of lipoproteins through that tissue. Studies already carried out have shown the existence of the gradient of rates and have demonstrated that the gradient is not due to the pulsatile nature of blood pressure or flow, since it is partially preserved in vitro under static conditions (9). The present paper reports studies