Role of endothelin-1 in myocardial failure.
Endothelin-1 (ET-1) is a potent molecule produced throughout the cardiovascular system; it can exert important effects on both the structure and function of vascular smooth muscle cells and cardiac myocytes. ET-1 appears to play a central role in the physiological regulation of cardiovascular function, particularly in the vasculature. The known actions of ET-1 and the demonstration that plasma ET-1 is elevated in patients with heart failure has raised the possibility that this molecule could play a role in the pathophysiology of heart failure. This thesis has been supported and furthered by studies in animal models of heart failure that demonstrate the salutary, short-term effects of ET-1 receptor antagonists on hemodynamic function, as well as improved ventricular remodeling and survival with long-term administration. Early clinical trials with these ET receptor blockers have demonstrated systemic vasodilation. Long-term trials to determine the effects of ET-1 blockade on symptoms and survival are under way.
Sam
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Boston Medical Center, MA 02118, USA.
Colucci
W S
WS
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000502:physiology; D000077300:Bosentan; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000072396:Endothelin-Converting Enzymes; D015870:Gene Expression; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D008666:Metalloendopeptidases; D010456:Peptides, Cyclic / Q000627:therapeutic use; D017466:Receptors, Endothelin / Q000502:physiology; D013449:Sulfonamides / Q000627:therapeutic use
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D013449:Sulfonamides; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)