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Hypertension, Vol 18, 132-141, Copyright © 1991 by American Heart Association
M Clozel, H Kuhn, F Hefti and HR Baumgartner
Hypertension is associated with an impairment of endothelium-dependent
relaxation. The angiotensin converting enzyme inhibitors captopril and
cilazapril can prevent this endothelial dysfunction. We recently observed
that long-term treatment with cilazapril could also prevent subendothelial
infiltration by mononuclear cells in spontaneously hypertensive rats. This
prompted us to examine whether, in spontaneously hypertensive rats,
endothelial dysfunction and subendothelial infiltration by mononuclear
cells are associated. These cells were characterized as monocyte
macrophages. Infiltration by monocyte macrophages was quantified by
morphometry. Endothelial function was estimated by calculating serotonin
ratio (maximal contraction to serotonin on isolated arterial rings with
endothelium over maximal contraction on paired rings without endothelium).
The regional distribution of endothelial dysfunction and subendothelial
monocyte macrophages was similar. Both were maximal in the carotid artery,
less in the aorta, and nonexistent in the renal artery. A 2- week treatment
with cilazapril decreased both endothelial dysfunction (serotonin ratio
decreased by 32%) and the number of subendothelial monocyte macrophages in
the aorta, which decreased by 38%. We conclude that in spontaneously
hypertensive rats, endothelial dysfunction and subendothelial monocyte
macrophage infiltration are associated and that cilazapril can decrease
both. The observation that angiotensin converting enzyme inhibitors affect
subendothelial accumulation of monocyte macrophage may lead to a better
understanding of the mechanism of action of this class of drugs.
ARTICLES
Endothelial dysfunction and subendothelial monocyte macrophages in hypertension. Effect of angiotensin converting enzyme inhibition
Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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