| Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries. | |
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MedLine Citation:
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PMID: 11535565 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulation Volume: 104 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2001 Sep |
Date Detail:
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Created Date: 2001-09-05 Completed Date: 2001-10-11 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 1114-8 Citation Subset: AIM; IM |
Affiliation:
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Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA. skinlay@rics.bwh.harvard.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Coronary Artery Disease
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physiopathology* Coronary Circulation / drug effects Coronary Vessels / drug effects, pathology, physiopathology* Endothelin-1 / physiology* Humans 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 | |
ID/Acronym/Agency:
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P50 HL48743/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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