• Reproductive toxicology · Aug 2015

    Review

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

    • Michiel Alexander de Raaf, Manon Beekhuijzen, Christophe Guignabert, Anton Vonk Noordegraaf, and Harm Jan Bogaard.
    • Pulmonary Hypertension Knowledge Center, Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
    • Reprod. Toxicol. 2015 Aug 15; 56: 45-51.

    AbstractThe 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. Copyright © 2015 Elsevier Inc. All rights reserved.

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