Macromolecular transport in the arterial intima: comparison of
chronic hypertension and lipopolysaccharide induced injuries.
Penn, Marc S., Shanthini Rangaswamy, Gerald M. Saidel, Guy M. Chisolm.
Department of Cell Biology, Cleveland Clinic Foundation, Cleveland,
Ohio 44195, Departments of Biomedical Engineering and Medicine, Case
Western Reserve University, Cleveland, Ohio 44106
APStracts 3:0482H, 1996.
Hypertension is a known risk factor for the development of
atherosclerosis, which is characterized by the abnormal accumulation
of low density lipoprotein and other plasma-borne macromolecules. The
goal of this study was to measure accumulation of a plasma-borne
macromolecular marker, horseradish peroxidase (HRP, 44kD), in the
aortic intima and media of chronically hypertensive rats. HRP
transport in two-year old spontaneously hypertensive rats (SHR) was
compared to that in age-matched Wistar-Kyoto (WKY) rats under
conditions in which blood pressures were not significantly different
during the 15 minute HRP circulation. Intimal accumulation and medial
HRP concentrations profiles were obtained from methacrylate embedded
sections after reaction with 3,3'-diaminobenzadine and H2O2. Data
were analyzed using mathematical models of macromolecular transport
to quantify the permeabilities of endothelium and internal elastic
lamina (IEL). Chronic hypertension increased endothelial permeability
without a change in IEL permeability. An apparent convective flux of
HRP into the intima of SHR raised intimal HRP to a concentration
higher than that of HRP in the plasma. Our results suggest that the
intimal accumulation of plasma-borne macromolecules from pressure
-driven convection is normally minimized by an intact endothelium.
Similar changes resulted from acute injury by lipopolysaccharide
suggesting endothelial injury could account for transport changes
associated with hypertension. After either chronic or acute
endothelial damage, transport of macromolecules into the intima
increases, but the IEL continues to retard transport of
macromolecules beyond the intima, resulting in increased intimal
accumulation.
Received 24 October 1996; accepted in final form 24 October 1996.
APS Manuscript Number H174-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996