Evidence for activation of endothelium and monocytes in
hypertensive rats.
Liu, Yong, Tane Liu, Richard M. McCarron, Maria Spatz, Giora
Feuerstein, John M. Hallenbeck, and Anna-Leena Sir[acute]en.
Department of Neurology, Uniformed Services University of the
Health Sciences,
APStracts 2:0370H, 1995.
We have proposed that an interaction between perivascular macrophages
and endothelium via cytokines could underlie the increased risk of
stroke in hypertension. Therefore, the activation of monocytes, the
endothelial expression of ICAM-1 and the numbers of monocyte/
macrophages in carotid arteries as well as the cytokine production in
carotid tissue of spontaneously hypertensive rats (SHR), normotensive
Wistar-Kyoto and Sprague-Dawley rats were studied. The total number
of blood monocytes (890+/-153 cells/mm3, n=10), and the number of
activated (nitroblue tetrazolium-positive) monocytes (220+/-51
cells/mm3, n=10) were significantly greater (p<0.05) in SHR than
in WKY rats (440+/-81 cells/mm3 and 40+/-16 cells/mm3, respectively,
n=10). Patchy endothelial expression of ICAM-1 was found in 77+/-9%
of carotid sections from stroke-prone SHR (SHR-SP, n=5) and in 75+/
-7% of the sections from SHR (n=7) but none of the sections from the
two normotensive rat strains (n=7). The number of endothelium
-attached monocyte/macrophages per millimeter of internal elastic
lamina was significantly greater in SHR-SP than in SHR (5.1+/-0.7,
n=4 and 3.3+/-0.3, n=6 p<0.05) while no monocytes were found
around the endothelium in either of the normotensive rat strains (n=7
in each group). Incubation of the SHR carotid arteries with
lipopolysaccharide (30-300 ng/ml) induced a concentration-dependent
expression of mRNAs for IL-1 and release of TNF-[alpha] to a
significantly greater degree than in the Wistar-Kyoto rats. The
results demonstrate that hypertension is associated with activation
of monocytes and endothelium and an increased endothelial adhesion
and subendothelial accumulation of monocyte/macrophages and with an
increased vascular capacity to produce cytokines.
Received 3 May 1995; accepted in final form 7 August 1995.
APS Manuscript Number H419-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.