Circulation, Vol 89, 2525-2532, Copyright © 1994 by American Heart Association
AM Zeiher, V Schachlinger, SH Hohnloser, B Saurbier and H Just
BACKGROUND: Abnormal vascular reactivity represents a fundamental
disturbance in vascular biology with the development of atherosclerosis.
Because endothelial vasodilator function plays a pivotal role in
controlling vasomotor tone, we hypothesized that atherosclerotic wall
thickening might directly interfere with deficient endothelium-mediated
dilation and thereby contribute to the abnormal reactivity of
atherosclerotic arteries in vivo. METHODS AND RESULTS: In 26 patients
without focal stenoses in the left anterior descending coronary artery,
acetylcholine (0.036 to 3.6 micrograms/mL) was infused into the artery to
evaluate endothelium-mediated vasodilation. Segmental vasomotor responses
to acetylcholine were correlated with the local extent of atherosclerotic
wall thickening quantitated by intracoronary ultrasound examination.
Seventeen of the patients also underwent cold pressor testing to assess the
vasoreactivity to sympathetic activation. The response of coronary artery
segments to acetylcholine varied from 35% dilation to 52% constriction and
demonstrated a segmental pattern, with dilation and constriction observed
in different segments of the same artery. The vasomotor response to
acetylcholine was closely correlated with the extent of local
atherosclerotic wall thickening (r = -.82, P < .0001). Over the entire
range of atherosclerotic wall thickening, segments from patients with
elevated high-density lipoprotein (HDL) cholesterol serum levels (> 75th
percentile) demonstrated a significantly blunted constrictor response to
acetylcholine (P < .01 at the maximal acetylcholine concentration)
compared with segments from patients with HDL cholesterol < 75th
percentile. The degree of constriction or dilation in response to the
acetylcholine infusion correlated with the response to cold pressor testing
(r = .75, P < .0001). Again, the cold pressor test-induced constrictor
response was significantly (P < .05) blunted in segments from patients
with elevated HDL cholesterol serum levels compared with those from
patients with HDL cholesterol < 75th percentile despite equal degrees of
atherosclerotic wall thickening. CONCLUSIONS: Coronary vasomotor responses
to the endothelium-dependent dilator acetylcholine and to sympathetic
stimulation by cold pressor test correlate with local atherosclerotic wall
thickening. Thus, the degree of abnormal local vascular reactivity is
closely related to the extent of atherosclerotic "plaque load" in human
epicardial arteries in vivo. Elevated HDL cholesterol serum levels
ameliorate abnormal vasoconstriction at any given extent of atherosclerotic
wall thickening, suggesting that HDL cholesterol exerts a beneficial effect
on abnormal vascular reactivity, a fundamental functional disturbance
associated with coronary atherosclerosis.
ARTICLES
Coronary atherosclerotic wall thickening and vascular reactivity in humans. Elevated high-density lipoprotein levels ameliorate abnormal vasoconstriction in early atherosclerosis
Department of Internal Medicine III, Universitatsklinik Freiburg, Germany.
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