TY - JOUR
T1 - Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension
AU - de Raaf, Michiel Alexander
AU - Beekhuijzen, Manon
AU - Guignabert, Christophe
AU - Vonk Noordegraaf, Anton
AU - Bogaard, Harm Jan
PY - 2015
Y1 - 2015
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.reprotox.2015.06.048
DO - https://doi.org/10.1016/j.reprotox.2015.06.048
M3 - Article
C2 - 26111581
SN - 0890-6238
VL - 56
SP - 45
EP - 51
JO - Reproductive toxicology (Elmsford, N.Y.)
JF - Reproductive toxicology (Elmsford, N.Y.)
ER -