Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension

Michiel Alexander de Raaf, Manon Beekhuijzen, Christophe Guignabert, Anton Vonk Noordegraaf, Harm Jan Bogaard

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)


The Pregnancy Prevention Program (PPP) is in place to prevent drug-induced developmental malformations. Remarkably, among the ten PPP-enlisted drugs are three endothelin-1 (ET-1) receptor antagonists (ERA's: ambrisentan, bosentan and macitentan), which are approved for the treatment of Pulmonary Arterial Hypertension (PAH). This review describes the effects of ERA's in PAH pathobiology and cardiopulmonary fetal development. While ERA's hamper pathological remodeling of the pulmonary vasculature and as such exert beneficial effects in PAH, they disturb fetal development of cardiopulmonary tissues. By blocking ET-1-mediated positive inotropic effects and myocardial fetal gene induction, ERA's may affect right ventricular adaptation to the increased pulmonary vascular resistance in both the fetus and the adult PAH patient. (C) 2015 Elsevier Inc. All rights reserved
Original languageEnglish
Pages (from-to)45-51
JournalReproductive toxicology (Elmsford, N.Y.)
Publication statusPublished - 2015

Cite this