Endothelin and endothelin receptor antagonists in heart failure

Endothelin (ET) is a recently discovered 21-amino acid peptide that has potent physiologic and pathophysiologic effects that appear to be involved in the development of heart failure. These include effects on arterial smooth muscle cells that cause intense peripheral vasoconstriction and stimulation of cardiac myocytes and fibroblasts. The latter promotes phenotypic changes in these cells that are consistent with cardiac remodeling. The effects of ET are mediated through interaction with two classes of cell surface receptors. The type A receptor (ET-A) has been associated with vasoconstriction and cell growth while the type B receptor (ET-B) has been associated with endothelial-cell mediated vasodilation and with the release of other neurohormones, such as aldosterone. This review summarizes evidence supporting the potential role of ET in the pathogenesis of heart failure and the available information concerning the use of ET receptor antagonists in treating this condition.