Circulation, Vol 79, 698-705, Copyright © 1989 by American Heart Association
JA Lopez, ML Armstrong, DJ Piegors and DD Heistad
In monkeys with early and advanced atherosclerosis, we examined responses
to the three major vasoactive agonists that are released when platelets
aggregate. Measurements were obtained in normal cynomolgus monkeys and in
monkeys fed an atherogenic diet for 4 +/- 1, 9 +/- 1, and 19 +/- 1 months
(mean +/- SEM). Morphometry of femoral and iliac arteries indicated that 4
months of atherogenic diet produced only slight intimal thickening, 9
months produced early lesions, and 19 months produced approximately 5-10
fold greater intimal proliferation than did 9 months of atherogenic diet.
Serotonin and adenosine 5'- diphosphate (ADP), which are
endothelium-dependent agonists, and adenosine and phenylephrine, which are
endothelium-independent agonists, were injected intra-arterially into the
perfused hind limb. Thromboxane A2 analogue U46619 also was studied.
Vasoconstrictor responses to serotonin were potentiated, and vasodilator
responses to ADP were impaired by early and advanced atherosclerosis. In
contrast, vasoconstrictor responses to phenylephrine and vasodilator
responses to adenosine were similar in all groups. Vasoconstrictor
responses to U46619 were potentiated by advanced atherosclerosis. Thus,
vascular responses to serotonin, ADP, and thromboxane A2 are altered by
atherosclerosis in a direction that would favor vasoconstriction when
platelets aggregate. Furthermore, because responses to endothelium-
dependent agonists are altered, these data suggest that endothelium is
dysfunctional in early atherosclerosis. These findings may explain, in
part, the propensity for exaggerated vasoconstriction even in arteries with
minimal atherosclerotic lesions.
ARTICLES
Effect of early and advanced atherosclerosis on vascular responses to serotonin, thromboxane A2, and ADP [published erratum appears in Circulation 1990 Jan;81(1):399]
Department of Internal Medicine, VA Medical Center, Iowa City, Iowa.
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