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

126 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

Fingerprint

Endothelin-1
Heart Failure
Vascular Resistance
Hemodynamics
Endothelins
Vasoconstriction
Vasodilation
Blood Vessels
Therapeutics
Endothelin-2
Endothelin-3
Exercise Tolerance
Brachial Artery
Epoprostenol
Left Ventricular Function
Cardiac Output
Dyspnea
Myocardial Ischemia
Endothelin Receptor Antagonists
Nitric Oxide

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Endothelin receptor antagonists in congestive heart failure : A new therapeutic principle for the future? / Lu, Tse Min; Tai, Ching Tai; Hsieh, Ming Hsiung; Tsai, Chin Feng; Lin, Yung Kuo; Yu, Wen Chung; Tsao, Hsuan Ming; Lee, Shih Huang; Ding, Yu An; Chang, Mau Song; Chen, Shih Ann.

In: Journal of the American College of Cardiology, Vol. 37, No. 6, 2001, p. 1493-1505.

Research output: Contribution to journalArticle

Lu, TM, Tai, CT, Hsieh, MH, Tsai, CF, Lin, YK, Yu, WC, Tsao, HM, Lee, SH, Ding, YA, Chang, MS & Chen, SA 2001, 'Endothelin receptor antagonists in congestive heart failure: A new therapeutic principle for the future?', Journal of the American College of Cardiology, vol. 37, no. 6, pp. 1493-1505. https://doi.org/10.1016/S0735-1097(01)01210-4
Lu, Tse Min ; Tai, Ching Tai ; Hsieh, Ming Hsiung ; Tsai, Chin Feng ; Lin, Yung Kuo ; Yu, Wen Chung ; Tsao, Hsuan Ming ; Lee, Shih Huang ; Ding, Yu An ; Chang, Mau Song ; Chen, Shih Ann. / Endothelin receptor antagonists in congestive heart failure : A new therapeutic principle for the future?. In: Journal of the American College of Cardiology. 2001 ; Vol. 37, No. 6. pp. 1493-1505.
@article{c416917e74624c418e5aaea259176480,
title = "Endothelin receptor antagonists in congestive heart failure: A new therapeutic principle for the future?",
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.",
author = "Lu, {Tse Min} and Tai, {Ching Tai} and Hsieh, {Ming Hsiung} and Tsai, {Chin Feng} and Lin, {Yung Kuo} and Yu, {Wen Chung} and Tsao, {Hsuan Ming} and Lee, {Shih Huang} and Ding, {Yu An} and Chang, {Mau Song} and Chen, {Shih Ann}",
year = "2001",
doi = "10.1016/S0735-1097(01)01210-4",
language = "English",
volume = "37",
pages = "1493--1505",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "6",

}

TY - JOUR

T1 - Endothelin receptor antagonists in congestive heart failure

T2 - A new therapeutic principle for the future?

AU - Lu, Tse Min

AU - Tai, Ching Tai

AU - Hsieh, Ming Hsiung

AU - Tsai, Chin Feng

AU - Lin, Yung Kuo

AU - Yu, Wen Chung

AU - Tsao, Hsuan Ming

AU - Lee, Shih Huang

AU - Ding, Yu An

AU - Chang, Mau Song

AU - Chen, Shih Ann

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035031967&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035031967&partnerID=8YFLogxK

U2 - 10.1016/S0735-1097(01)01210-4

DO - 10.1016/S0735-1097(01)01210-4

M3 - Article

VL - 37

SP - 1493

EP - 1505

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 6

ER -