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Type: Journal article
Title: Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries
Author: Kinlay, S.
Behrendt, D.
Wainstein, M.
Beltrame, J.
Fang, J.
Creager, M.
Selwyn, A.
Ganz, P.
Citation: Circulation, 2001; 104(10):1114-1118
Publisher: Lippincott Williams & Wilkins
Issue Date: 2001
ISSN: 0009-7322
Statement of
Scott Kinlay, Dominik Behrendt, Marco Wainstein, John Beltrame, James C. Fang, Mark A. Creager, Andrew P. Selwyn, and Peter Ganz
Abstract: Background - Atherosclerotic coronary arteries are prone to constriction but the underlying causes are incompletely understood. We tested the hypothesis that endothelin-1 (ET-1), a potent vasoconstrictor, contributes to the heightened tone of atherosclerotic human coronary arteries. Methods and Results - In 8 patients with coronary artery disease (CAD) and 8 patients with angiographically smooth coronary arteries (normal), we infused BQ-123, an antagonist of the ETA receptor, into a major coronary artery (infused artery) at 40 nmol/min for 60 minutes. The infused artery in the CAD patients contained a >50% stenosis. Using quantitative angiography, we compared the dilation of the infused artery with another, noninfused coronary artery. To estimate the magnitude of the contribution of ET-1 to coronary tone, we compared the dilation to BQ-123 with that elicited by intracoronary nitroglycerin (200 µg). BQ-123 induced significant dilation in the normal arteries (7.3% at 60 minutes, P<0.001 versus noninfused arteries) and a greater dilation in the CAD arteries (16.3% at 60 minutes, P<0.001 versus infused normal arteries). The dilation at stenoses was particularly pronounced (21.6% at 60 minutes, P<0.001 versus infused CAD arteries). Compared with the dilation from nitroglycerin, ET-1 contributed to 39% of the coronary tone in normal arteries, 74% of tone in CAD arteries, and 106% of tone at stenoses (P<0.01). Conclusions - ET-1 accounts for nearly all the resting tone in atherosclerotic coronary arteries, especially at stenoses. Inhibitors of ET-1, by relieving constriction, may significantly lessen the hemodynamic significance of coronary stenoses and thereby reduce myocardial ischemia.
Keywords: Endothelin
Rights: © 2001 American Heart Association, Inc.
DOI: 10.1161/hc3501.095707
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