Circulation, Vol 84, 1273-1278, Copyright © 1991 by American Heart Association
JM McLenachan, JK Williams, RD Fish, P Ganz and AP Selwyn
BACKGROUND. Healthy arteries exhibit endothelium-dependent dilation in
response to both local acetylcholine and increased blood flow. In humans,
clinically overt coronary artery disease is characterized by loss of
dilation to both acetylcholine and blood flow. The temporal relation,
however, between functional abnormalities of the endothelium and the
development of atherosclerosis has not been established. METHODS AND
RESULTS. We examined endothelial vasodilator function in vivo at an early
stage of the development of atherosclerosis. Two groups of seven Macaca
fascicularis monkeys were studied; one group was fed a high cholesterol
diet (0.73-1.0 mg cholesterol per calorie) for 11 months. Cholesterol
feeding was associated with increased plasma cholesterol levels and with
intimal thickening of the iliac arteries but with no reduction in luminal
diameter. Endothelium-dependent vasomotor responses of the iliac arteries
were then examined in vivo by quantitative contrast angiography.
Acetylcholine produced significant dilation in the controls but paradoxical
constriction in the group with early atherosclerosis (+9.0 +/- 3.2% versus
-5.3 +/- 5.4%, p less than 0.05). In response to a twofold increase in
blood flow achieved by administering adenosine distal to the arterial
segment under examination, the controls again dilated, whereas the
atherosclerotic group failed to dilate (+ 11.6 +/- 2.1% versus + 0.5 +/-
2.4%, p less than 0.05). Both groups, however, were able to dilate, and
dilated equally, to the nonendothelium-dependent agent nitroglycerin (+
13.7 +/- 4.8% versus + 19.1 +/- 4.3%, NS). CONCLUSIONS.
Endothelium-dependent vasodilation in response to both acetylcholine and
increased blood flow may be lost early in the course of developing
atherosclerosis before the appearance of stenosing and occlusive disease.
ARTICLES
Loss of flow-mediated endothelium-dependent dilation occurs early in the development of atherosclerosis
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
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