(Circulation. 1996;94:604-606.)
© 1996 American Heart Association, Inc.
Articles |
Is There a Role for Endothelin in the Natural History of Heart Failure?
the Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis.
Correspondence to Jay N. Cohn, MD, Cardiovascular Division, University of Minnesota Medical School, Box 508 UMHC, 420 Delaware St SE, Minneapolis, MN 55455. E-mail cohnx001@maroon.tc.umn.edu.
Key Words: Editorials • endothelin • heart failure
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Introduction |
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A role for locally released and circulating peptides in the progressive syndrome of heart failure has been widely entertained because of the evidence for activation of a number of these hormonal systems in experimental and clinical studies and because a satisfactory explanation for the progressive cardiac and vascular functional abnormalities in heart failure has remained elusive. Endothelin (ET) is a particularly attractive candidate because it is released by the endothelium, which is thought to be functionally abnormal in heart failure,1 2 3 and because it is a potent vasoconstrictor and growth promoter.4 5 Since vasoconstriction and myocardial and vascular growth and remodeling may characterize the syndrome,6 7 8 excess endothelin release could serve an important role in the initiation or perpetuation of these processes.
Shimoyama and his associates9 report in this issue of Circulation that the nonspecific endothelin receptor (ETA and ETB) antagonist bosentan exerted a vasodilator effect in their canine model of chronic left ventricular dilation that resulted from repeated coronary embolization. Because this vasodilator effect was not demonstrable in normal dogs, the authors appropriately suggest that the endothelin system appears to be upregulated in their canine model. The very modest increases in circulating levels of ET-1 they report in this model may not be pertinent because the peptide may act largely as a local hormone. Indeed, the striking rise in circulating ET-1 levels after receptor blockade confirms the active synthetic pathway. They speculate from these data that endothelin blockade may be a useful form of therapy for heart failure.
Such observations have
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