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

研究成果: 雜誌貢獻回顧型文獻同行評審

133 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)1493-1505
頁數13
期刊Journal of the American College of Cardiology
37
發行號6
DOIs
出版狀態已發佈 - 2001
對外發佈Yes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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