Inhibition of myocardial endothelin pathway improves long-term survival in heart failure

Nature volume 384, pages353–355(1996)Cite this article

Abstract

OCCLUSION of the diseased coronary artery in humans causes acute myocardial infarction, survivors of which have a high risk for the development of chronic heart failure1. Cardiac myocytes and vascular endothelial cells produce endothelin-1 (refs 2–4), which increases the contractility of cardiac muscle and of vascular smooth muscle cells2,3,5. Endothelin-1 also exerts long-term effects such as myocardial hypertrophy, and causes cellular injury in cardiac myocytes3,5–7. Production of endothelin-1 is markedly increased in the myocardium of rats with heart failure, and acute application of an endothelin-receptor antagonist decreases myocardial contractility in such rats, indicating that myocardial endothelin-1 may help to support contractility of the failing heart8. But we report here that the upregulated myocardial endothelin system may contribute to the progression of chronic heart failure, because long-term treatment with an endothelin-receptor antagonist greatly improved the survival of rats with chronic heart failure. This beneficial effect was accompanied by significant amelioration of left ventricular dysfunction and prevention of ventricular remodelling, in which there is usually an increase in the ventricular mass and cavity enlargement of the ventricle.

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Affiliations

  1. Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305, Japan

    Satoshi Sakai, Takashi Miyauchi, Iwao Yamaguchi & Yasuro Sugishita

  2. Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305, Japan

    Katsutoshi Goto

  3. Tsukuba Research Institute, Banyu Pharmaceutical Co., Tsukuba, Ibaraki, 300–33, Japan

    Masahiko Kobayashi

Authors
  1. Satoshi Sakai
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  2. Takashi Miyauchi
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  3. Masahiko Kobayashi
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  4. Iwao Yamaguchi
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  5. Katsutoshi Goto
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  6. Yasuro Sugishita
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Sakai, S., Miyauchi, T., Kobayashi, M. et al. Inhibition of myocardial endothelin pathway improves long-term survival in heart failure. Nature 384, 353–355 (1996). https://doi.org/10.1038/384353a0

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