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Clinical Pharmacology of Endothelin Receptor Antagonists Used in the Treatment of Pulmonary Arterial Hypertension

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Abstract

Pulmonary arterial hypertension (PAH) is a devastating life-threatening disorder characterized by elevated pulmonary vascular resistance leading to elevated pulmonary arterial pressures, right ventricular failure, and ultimately death. Vascular endothelial cells mainly produce and secrete endothelin (ET-1) in vessels that lead to a potent and long-lasting vasoconstrictive effect in pulmonary arterial smooth muscle cells. Along with its strong vasoconstrictive action, ET-1 can promote smooth muscle cell proliferation. Thus, ET-1 blockers have attracted attention as an antihypertensive drug, and the ET-1 signaling system has paved a new therapeutic avenue for the treatment of PAH. We outline the current understanding of not only the pathogenic role played by ET-1 signaling systems in the pathogenesis of PH but also the clinical pharmacology of endothelin receptor antagonists (ERA) used in the treatment of PAH.

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Conflict of interest

M.C. Chaumais, C. Guignabert, and A. Boucly have no conflicts of interest to declare. L. Savale has relationships with pharmaceutical companies, including Actelion, Pfizer, GSK, and Lilly. Relationships include consulting services and fees for speaking. X. Jaïs has received honorarium for consulting services from Actelion, Pfizer, and GSK. D. Montani has received honorarium for consultancy services from Actelion, Pfizer, Bayer, and GSK. G. Simonneau has relationships with pharmaceutical companies including Actelin, Bayer, GSK, Novartis, and Pfizer. Relationships include consultancy services and membership of scientific advisory boards. M. Humbert has relationships with pharmaceutical companies including Actelion, Bayer, GSK, Novartis, and Pfizer. In addition to being investigator in trials involving these companies, relationships include consultancy services, membership of scientific advisory boards, fees for speaking, funds for research, and reimbursement for attending symposia. O. Sitbon has relationships with pharmaceutical companies including Actelion, Bayer, GSK, Pfizer, and United Therapeutics. In addition to being investigator in trials involving these companies, relationships include consultancy services, membership of scientific advisory boards, fees for speaking, and reimbursement for attending symposia.

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Authors and Affiliations

  1. Faculté de Pharmacie, Univ. Paris-Sud, Châtenay Malabry, France

    Marie-Camille Chaumais

  2. INSERM UMR_S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France

    Marie-Camille Chaumais, Christophe Guignabert, Laurent Savale, Xavier Jaïs, David Montani, Gérald Simonneau, Marc Humbert & Olivier Sitbon

  3. AP-HP, Service de Pharmacie, Département Hospitalo-Universitaire (DHU) Thorax Innovation, Hôpital Antoine Béclère, Clamart, France

    Marie-Camille Chaumais

  4. Faculté de Médecine, Univ. Paris-Sud, Le Kremlin-Bicêtre, France

    David Montani, Gérald Simonneau, Marc Humbert & Olivier Sitbon

  5. AP-HP, Centre de Référence de l’Hypertension Pumonaire Sévère, Département Hospitalo-Universitaire (DHU) Thorax Innovation, Service de Pneumologie et, Hôpital Bicêtre, Le Kremlin-Bicêtre, France

    Laurent Savale, Xavier Jaïs, Athénaïs Boucly, David Montani, Gérald Simonneau, Marc Humbert & Olivier Sitbon

  6. Service de Pneumologie et Soins Intensifs, Hôpital Universitaire de Bicêtre, 78, rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France

    Olivier Sitbon

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  1. Marie-Camille Chaumais
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  2. Christophe Guignabert
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  3. Laurent Savale
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  8. Marc Humbert
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  9. Olivier Sitbon
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Correspondence to Olivier Sitbon.

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Chaumais, MC., Guignabert, C., Savale, L. et al. Clinical Pharmacology of Endothelin Receptor Antagonists Used in the Treatment of Pulmonary Arterial Hypertension. Am J Cardiovasc Drugs 15, 13–26 (2015). https://doi.org/10.1007/s40256-014-0095-y

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