MACROMOLECULAR TRANSPORT IN THE ARTERIAL INTIMA - COMPARISON OF CHRONIC AND ACUTE INJURIES

Hypertension is a known risk factor for the development of atheroscler osis, which is characterized by the abnormal accumulation of low-densi ty lipoprotein and other plasma-borne macromolecules. The goal of this study was to measure accumulation of a plasma-borne macromolecular ma rker, horseradish peroxidase (HRP; 44 kDa), in the aortic intima and m edia of chronically hypertensive rats. HRP transport in 2-yr-old spont aneously hypertensive rats (SHR) was compared with that in age-matched Wistar-Kyoto rats (WKY) under conditions in which blood pressures wer e not significantly different during the 15-min HRP circulation. Intim al accumulation and medial HRP concentration profiles were obtained fr om methacrylate-embedded sections after reaction with 3,3'-diaminobenz idine and H2O2. Data were analyzed using a mathematical model of macro molecular transport to quantify the permeabilities of endothelium and internal elastic lamina (IEL). Chronic hypertension increased endothel ial permeability without a change in IEL permeability. An apparent con vective flux of HRP into the intima of SHR raised intimal HRP to a con centration higher than that of HRP in the plasma. Our results suggest that the intimal accumulation of plasma-borne macromolecules from pres sure-driven convection is normally minimized by an intact endothelium. Similar changes resulted from acute injury by lipopolysaccharide, sug gesting endothelial injury could account for transport changes associa ted with hypertension. After either chronic or acute endothelial damag e, transport of macromolecules into the intima increases, but the IEL continues to retard transport of macromolecules beyond the intima, res ulting in increased intimal accumulation.