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Endothelin and endothelin antagonists: Potential role in cardiovascular and renal disease

  • Chapter
Book cover Biochemistry of Signal Transduction in Myocardium

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 17))

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Abstract

Endothelin-1 is a recently discovered peptide mainly released from endothelial cells. Hypoxia and ischemia as well as numerous factors such as angiotensin 11, thrombin and transforming growth factor β1 stimulate the fomation of the peptide. On the other hand the synthesis of endothelin is inhibited by nitric oxide and atrial natriuretic peptide via the formation of cyclic guanosine monophosphate. Released from endothelial cells endothelin-1 mediates transient vasodilation followed by a profound and longlasting vasoconstriction. Endothelin is also a mitogen for smooth muscle proliferation. Endothelins exert their biological effects via activation of specific receptors. Two different receptors have been cloned from mammalian tissues (ETA and ETB receptors). On vascular smooth muscle cells both receptors mediate contractions. Endothelial cells only express ETB receptors linked to the formation of nitric oxide and/or prostacyclin formation. Increased plasma concentrations of endothelin-1 have been described in a variety of diseases such as pulmonary hypertension, arteriosclerosis, renal failure, acute coronary syndromes, heart failure, migraine and vascular diseases.

Recently an increasing number of endothelin receptor antagonists have been synthetized, which have been shown to inhibit endothelin-mediated vasoconstriction. Clinical studies are now ongoing to elucidate the pathophysiologic role of endothelin and the potential benefit of the blockade of the system in different disease states.

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Authors and Affiliations

  1. Cardiology, Cardiovascular Research University Hospital, Inselspital, CH-3010, Bern, Switzerland

    G. Noll, R. R. Wenzel & T. F. Lüscher

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  1. G. Noll
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  2. R. R. Wenzel
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  3. T. F. Lüscher
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Editors and Affiliations

  1. Department of Biochemistry, Cardiovascular Research Institute COEUR, Faculty of Medicine of Health Science, Erasmus University Rotterdam, P.O. Box 1738, 3300 DR, Rotterdam, The Netherlands

    Jos M. J. Lamers

  2. Department of Cardiology, Cardiovascular Research Institute COEUR, Erasmus University Rotterdam, P.O. Box 1738, 3300 DR, Rotterdam, The Netherlands

    Pieter D. Verdouw

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© 1996 Kluwer Academic Publishers

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Noll, G., Wenzel, R.R., Lüscher, T.F. (1996). Endothelin and endothelin antagonists: Potential role in cardiovascular and renal disease. In: Lamers, J.M.J., Verdouw, P.D. (eds) Biochemistry of Signal Transduction in Myocardium. Developments in Molecular and Cellular Biochemistry, vol 17. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1275-8_34

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  • DOI: https://doi.org/10.1007/978-1-4613-1275-8_34

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8544-1

  • Online ISBN: 978-1-4613-1275-8

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