Endothelin Receptor Antagonists in Cardiovascular Medicine: Challenges and Opportunities

  • Matthias BartonEmail author


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.


Pulmonary Arterial Hypertension Proteinuric Renal Disease Primary Pulmonary Arterial Hypertension Antagonist Darusentan 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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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Copyright information

© Springer-Verlag London Limited 2012

Authors and Affiliations

  1. 1.Molecular Internal Medicine, LTK Y44 G22University of ZurichZürichSwitzerland

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