Transendothelial macromolecular transport in the aorta of spontaneously hypertensive rats.
Leaky endothelial junctions occurring during cell turnover have been postulated to be a major pathway for enhanced lipoprotein transport across the vascular endothelial layer, which leads to the development of atherosclerosis. Because hypertension has been well documented as one of the major risk factors for atherosclerosis, we explored the possibility that hypertension accelerates atherogenesis by increasing the turnover of endothelial cells and hence the transendothelial macromolecular permeability. The investigations were performed on thoracic aortas of 10 male 3-4-month-old spontaneously hypertensive rats and eight male age-matched Wistar-Kyoto normotensive rats. In en face preparations of aortic specimens, mitotic endothelial cells were identified by hematoxylin nuclear staining; dying or dead endothelial cells containing cytoplasmic immunoglobulin G were detected by indirect immunoperoxidase technique; and endothelial leakage to Evans blue-albumin conjugate was visualized by fluorescence microscopy. The number of leaky foci per unit endothelial surface area in spontaneously hypertensive rats was found to be approximately three times that in Wistar-Kyoto control rats; the frequencies of both endothelial cell mitosis and death in spontaneously hypertensive rats were also approximately three times the corresponding values in Wistar-Kyoto rats. These findings indicate that hypertension in spontaneously hypertensive rats is accompanied by increased endothelial cell turnover and an attendant enhancement of permeability to macromolecules.