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Specific inhibition of AT1‐AAs by direct binding improves maternal and fetal outcome in response to placental ischemia during pregnancy: emphasizing the importance of novel drug development in the treatment of preeclampsia (860.15)
Author(s) -
Moseley Janae,
Castillo Javier,
Amaral Lorena,
Cornelius Denise,
LaMarca Babbette
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.860.15
Subject(s) - preeclampsia , angiotensin ii receptor type 1 , pregnancy , medicine , blood pressure , fetus , endocrinology , gestation , proteinuria , angiotensin ii , biology , kidney , genetics
Preeclampsia, (PE) hypertension with proteinuria during pregnancy, is associated with antibodies that activate the angiotensin II receptor (AT1‐AA). Infusion of AT1‐AA increases blood pressure (MAP) and causes many characteristics of PE in pregnant rodents. The objective of the study was to determine if specific inhibition of AT1‐AA improves pregnancy outcomes in RUPP pregnant rat model of PE. Specifically AT1‐AA inhibitory peptide (2ug/ml saline) was infused via miniosmotic pumps into RUPP rats beginning day 14 of gestation, immediately following the RUPP procedure. On day 19 blood pressure, MAP, blood and tissue were collected. MAP was 99+/‐2 in NP(n=18), 121+/‐2 in control RUPP rats (n=19;P<0.001) and was 109 +/‐6 mmHg (n=9 P<0.02) in RUPPs + AT1‐AA inhibitory peptide. Pup weight in NP was 2.4 +/‐ 0.04 in NP; 1.9 +/‐ 0.06 in RUPP, improved significantly to 2.2 +/‐ 0.14 g (P<0.05) in RUPPs + AT1‐AA inhibitory peptide.These studies indicate that specific AT1‐AA inhibition improves maternal blood pressure and fetal outcome in response to placental ischemia, thereby emphasizing the importance of drug discovery for AT1‐AA inhibition to improve pregnancy outcomes in preeclamptic patients. Grant Funding Source : Ferring Pharmaceuticals, NIH NICHD