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Placenta ischemia, the initiating event in preeclampsia (PE), is associated with fetal growth restriction. Inhibition of the agonistic autoantibody against the angiotensin type 1 receptor AT

The seven amino acid inhibitory peptide to the AT1-AA ('n7AAc') has limited transfer to the fetus at gestational day 20, improves uterine blood flow and fetal growth in the reduced uterine perfusion pressure model of preeclampsia (PE), and does not impair fetal survival during gestation in sham-operated or placental ischemic rats. Collectively, these findings suggest that maternal administration of 'n7AAc' as an effective strategy for the treatment of PE is associated with improved outcomes in the fetus.

Preeclampsia (PE), new onset hypertension during pregnancy, is the leading cause of death and morbidity for the mother and low birth weight in offspring. PE women have activated B cells producing agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA). We have shown Rituximab (R), used clinically for B cell depletion, lowers mean arterial pressure (MAP), B cells, and AT1-AA in the RUPP rat model of PE. Clinical studies show no untoward effects on offspring of pregnant women maintained on R for treating lymphoma, however, R is not used during PE therefore, effects of maternal B cell depletion on offspring survival and growth in response to placental ischemia is unknown. We hypothesize that R will deplete maternal B cells in RUPP rats without worsening the effect of placental ischemia on pup growth and survival. To test this hypothesis, R (250 mcg/kg) was given on gestation day (GD) 14 via mini-osmotic pump. On GD 19 B cells were measured by flow cytometry, and MAP and pup weights were recorded. A separate group of dams were allowed to deliver, pup weights were recorded within 12 hours and weekly until 16 weeks, and B cells were analyzed. A one-way ANOVA was used for statistical analysis. MAP increased in RUPP 123±2 (n=19, p

Placenta ischemia, the initiating factor in preeclampsia (PE), is associated with intrauterine growth restriction (IUGR) and increased blood pressure (BP) in offspring. Yet, the only treatment for PE is delivery of the baby and placenta. The Reduced Uterine Perfusion Pressure (RUPP) rat model induced by placental ischemia at gestational day 14 (G14) mimics many facets of human PE including pregnancy-specific hypertension, an increase in the agonistic ANG II Type 1 receptor autoantibody (AT1-AA), IUGR and increased BP in the offspring. Inhibition of AT1-AA using an epitope-binding inhibitory peptide ('n7AAc') attenuates increased BP at gestational day 19 in the RUPP. Yet, whether use of ‘n7aac’ improves fetal growth and mitigates increased BP in the offspring is unknown. Thus, we tested the hypothesis that maternal administration of ‘n7aac’ improves fetal growth by attenuating reduced uterine blood flow and impaired placental remodeling. Sham or RUPP surgery was performed at G14 with administration of vehicle or ‘n7aac’ (144μg/day) via mini osmotic pump until gestational day 20 (G20). At G20 uterine artery resistance index was significantly elevated in vehicle RUPP (0.69±0.02 mm/s n=10) compared to vehicle Sham (0.48±0.02 mm/s n=8) (P