Endothelin receptor antagonist has limited access to the fetal compartment during chronic maternal administration late in pregnancy

Endothelin receptor A (ETA) antagonism normalizes fetal growth in several models of rodent fetal growth restriction (FGR). Our aims were to determine the levels of ETA antagonist in maternal and fetal plasma following chronic maternal administration, and to determine its impact on pregnancy outcome, survival and growth of rat pups. Timed pregnant rats were treated with one of two endothelin receptor antagonists or vehicle, from gestation day 14–21 (term=22days). The antagonists and their respective doses were ABT-546 (20mg/kg/day) and FR139317 (12mg/kg/day). On day 21, in six rats per group, maternal and fetal plasma ABT-546 was assayed by HPLC. Five additional rats in each group delivered spontaneously and nursed their pups through postpartum day 7. Viability of newborns, oxygen saturation, litter sizes, and pup weights were recorded on postpartum days 1 and 7. Fetal antagonist levels reached only 2% of maternal levels (p