Effect of Age on the Pattern of Short-term Albumin Uptake by the Rabbit Aortic Wall Near Intercostal Branch Ostia

Abstract

Abstract Lipid deposition occurs more frequently downstream than upstream of branches in immature human aorta but the opposite pattern is seen in mature vessels. These distributions may reflect variation in the uptake of plasma macromolecules by the aortic wall. We have recently shown that the quasi–steady state uptake of albumin is greater downstream than upstream of branches in immature rabbit aortas and that the opposite pattern occurs in mature animals. Additionally, there is a sharp drop in the mean uptake shortly after weaning. In the present study, the mechanisms underlying these phenomena were investigated by examining the short-term uptake of albumin and its distribution across the wall. Albumin was labeled with a fluorescent dye and introduced into the circulation of conscious New Zealand White rabbits. Thoracic aortas were fixed in situ 10 minutes later and were sectioned through the center of intercostal ostia. Fluorescence from sections was measured by using digital imaging fluorescence microscopy and was converted to tracer concentrations after appropriate autofluorescence levels had been subtracted. In animals aged 45 days, more tracer was detected in the wall downstream than upstream of branches; the difference between regions was >100% of the mean value. This percentage halved and the mean uptake decreased almost threefold by 75 days. In mature animals, the mean value remained at the 75-day level but the converse distribution was seen; 22% more tracer was detected upstream than downstream. These trends were insensitive to the depth of the intimal-medial layer examined. In each region, the maximum tracer concentration occurred close to the luminal surface but not always within the first 2.9-μm-thick layer of the wall. Maxima were similar in magnitude to those observed at quasi–steady state, but the fall with increasing distance into the wall was much sharper. In many cases concentrations remained constant over most of the media, and rises toward the adventitial boundary were rarely seen. Uptake after 10 minutes predominantly reflects the rate at which tracer enters the wall. The concentration profiles were consistent with most of the tracer having entered from the luminal surface and with the involvement of convective transport. The trends observed with age closely paralleled those occurring at quasi–steady state. Consequently, the latter are also likely to be determined by changes in the resistance of the wall to macromolecule influx.