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Translational Vascular Medicine pp 231–259Cite as

Endothelin Receptor Antagonists in Cardiovascular Medicine: Challenges and Opportunities

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Abstract

The discovery of the release of endothelium-derived vasoconstriction led to studies identifying the endothelium-derived peptide endothelin and its receptors. In the early 1990s, endothelin receptor antagonists (ERAs) were developed and preclinical and clinical studies initiated. Despite strong experimental evidence for a role of endothelin-1, the predominant member of the endothelin peptide family, in cardiovascular physiology and disease, the vast majority of clinical studies in cardiovascular medicine using endothelin receptor antagonists (ERAs) were negative partly because study design and/or patient selection were frequently inadequate. This chapter provides an overview of the endothelin system as well as preclinical data of ERA studies obtained in disease models of arterial hypertension, atherosclerosis, coronary artery disease, pulmonary hypertension, heart failure, renal disease, and allograft rejection following cardiac transplantation. Results and developments in ERA clinical trials in cardiovascular medicine will be discussed also covering reasons for failed ERA trials and discontinuation of clinical drug development of numerous ERAs.

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Acknowledgments

This work was supported by grants from the Swiss National Science Foundation (Nr. 108 258 and 122 504). I thank present and former members of my laboratory as well as my collaborators who have contributed to the original research discussed in this chapter.

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  1. Molecular Internal Medicine, LTK Y44 G22, University of Zurich, Zürich, Switzerland

    Matthias Barton

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  1. University College London, Gower Street, London, WC1E 6BT, United Kingdom

    David Abraham

  2. The Royal Free & Univ College Med School, Gower Street, London, WC1E 6BT, United Kingdom

    Clive Handler

  3. University College London, Gower Street, London, WC1E 6BT, United Kingdom

    Michael Dashwood

  4. The Royal Free & Univ College Med School, Gower Street, London, WC1E 6BT, United Kingdom

    Gerry Coghlan

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Barton, M. (2012). Endothelin Receptor Antagonists in Cardiovascular Medicine: Challenges and Opportunities. In: Abraham, D., Handler, C., Dashwood, M., Coghlan, G. (eds) Translational Vascular Medicine. Springer, London. https://doi.org/10.1007/978-0-85729-920-8_15

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