Endothelin Receptor Antagonists (ERA) in Hypertension and Chronic Kidney Disease: a Rose with Many Thorns

Doumas M1, 2, *, Athyros V1, Katsiki N1, Reklou A1, Lazaridis A1, Karagiannis A1
1 2nd Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
2 VAMC and George Washington University, Washington, DC, USA

© 2013 Doumas et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the 49 Konstantinoupoleos street, Hippokration Hospital, 54643 Thessaloniki, Greece; Tel: +30 2310992836; Fax: +30 2310992834; E-mail:


The discovery of endothelin created a lot of enthusiasm and paved new therapeutic avenues for the treatment of arterial hypertension. Endothelin plays a significant role in blood pressure regulation through pronounced vasoconstriction and modulation of sodium and water reabsorption in the kidneys. Endothelin receptor antagonists have been tested in many clinical trials in patients with arterial hypertension, heart failure, pulmonary arterial hypertension, systemic sclerosis, chronic kidney disease, and diabetic nephropathy. However, the results were usually disappointing, except in pulmonary hypertension and scleroderma digital ulcers. The future of ERAs for the treatment of arterial hypertension and chronic kidney disease does not seem bright, and only the combination with other classes of antihypertensive drugs might offer a way out.

Keywords: Endothelin, endothelin receptor antagonists, hypertension, chronic kidney disease, heart failure, pulmonary hypertension, pre-eclampsia, antineoplastic agents.