Endothelin receptor antagonists in congestive heart failure: A new therapeutic principle for the future?

Tse Min Lu, Ching Tai Tai, Ming Hsiung Hsieh, Chin Feng Tsai, Yung Kuo Lin, Wen Chung Yu, Hsuan Ming Tsao, Shih Huang Lee, Yu An Ding, Mau Song Chang, Shih Ann Chen

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Congestive heart failure (CHF) is characterized by impaired left ventricular function, increased peripheral and pulmonary vascular resistance and reduced exercise tolerance and dyspnea. Thus, mediators involved in the control of myocardial function and vascular tone may be involved in its pathophysiology. The family of endothelins (ET) consists of four closely related peptides, ET-1, ET-2, ET-3 and ET-4, which cause vasoconstriction, cell proliferation and myocardial effects through activation of ETA receptors. In contrast, endothelial ETB receptors mediate vasodilation via release of nitric oxide and prostacyclin. In addition, ETB receptors in the lung are a major pathway for the clearance of ET-1 from plasma. Thus, infusion of an ETA-receptor antagonist into the brachial artery in healthy humans leads to vasodilation, whereas infusion of an ETB-receptor antagonist causes vasoconstriction. Endothelin-1 plasma levels are elevated in CHF and correlate both with hemodynamic severity and symptoms. Plasma levels of ET-1 and its precursor, big ET-1, are strong independent predictors of death after myocardial infarction as well as in CHF. Endothelin-1 contributes to increased systemic and pulmonary vascular resistance, vascular dysfunction, myocardial ischemia and renal impairment in CHF. Selective ETA, as well as combined ETA/B-receptor antagonists, have been studied in patients with CHF, and their use has shown impressive hemodynamic improvement (i.e., reduced peripheral vascular and pulmonary resistance as well as increased cardiac output). These results indicate that ET-receptor antagonists, indeed, have a potential to improve hemodynamics, symptoms and, potentially, prognosis in patients with CHF, which still carries a high mortality.

Original languageEnglish
Pages (from-to)1493-1505
Number of pages13
JournalJournal of the American College of Cardiology
Volume37
Issue number6
DOIs
Publication statusPublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Nursing(all)

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