Document Detail

Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries.
MedLine Citation:
PMID:  11535565     Owner:  NLM     Status:  MEDLINE    
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 ET(A) 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 microgram). 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.
S Kinlay; D Behrendt; M Wainstein; J Beltrame; J C Fang; M A Creager; A P Selwyn; P Ganz
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  104     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-09-05     Completed Date:  2001-10-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1114-8     Citation Subset:  AIM; IM    
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
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MeSH Terms
Coronary Artery Disease / physiopathology*
Coronary Circulation / drug effects
Coronary Vessels / drug effects,  pathology,  physiopathology*
Endothelin-1 / physiology*
Middle Aged
Multivariate Analysis
Nitroglycerin / pharmacology
Peptides, Cyclic / pharmacology
Receptor, Endothelin A
Receptors, Endothelin / antagonists & inhibitors
Vasoconstriction / drug effects,  physiology*
Vasodilator Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Endothelin-1; 0/Peptides, Cyclic; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 0/Vasodilator Agents; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu); 55-63-0/Nitroglycerin

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