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Blockade Of The ET A Receptor In An Animal Model Of HELLP Syndrome
Author(s) -
Wallace Kedra,
Spencer Shauna,
Kyle Patrick,
Moseley Janae,
Morris Rachael
Publication year - 2015
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.29.1_supplement.968.23
Subject(s) - endocrinology , medicine , hellp syndrome , preeclampsia , endothelin receptor , creatinine , endothelin 1 , blockade , gestational hypertension , receptor , hemolysis , receptor antagonist , antagonist , pregnancy , biology , genetics
Women with hypertensive forms of pregnancy such as hemolysis‐elevated liver enzymes‐low platelet‐syndrome have increased circulating levels of endothelin‐1 (ET‐1), however the relationship between hypertension and ET‐1 in this hypertensive disorder of pregnancy has not been studied. Using an animal model of hemolysis elevated liver enzyme low platelet (HELLP) syndrome we sought to determine if along with the hypertension that occurs in this animal model if there was increased activation/dysfunction of ET‐1 and if blockade of the endothelin‐1 receptor‐A (ET A ) attenuated hypertension. On gestational day (GD) 12 timed‐pregnant rats were infused with sFlt‐1 and sEng (4.7 and 7µg/kg) via mini‐osmotic pumps for 8 days. A subset of rats were treated with ET A antagonist (ABT‐627, 5mg/kg) for 8 days. Rats with HELLP had significantly increased hypertension (P=0.0001), circulating ET‐1 (P=0.03) and a significant 3.3 and 7.2‐fold increase in pre‐proendothelin (PPET) mRNA placenta and liver expression (P=0.01; P=0.04). Urinary protein:creatinine (PC) ratio was significantly increased in these animals (P=0.0007) and circulating factors from these rats stimulated a significant increase in endothelial cell ET‐1 secretion (P=0.001) in an in vitro assay. Blockade of the ET A receptor significantly decreased hypertension (P=0.001), circulating ET‐1 (P=0.004), placental PPET mRNA expression (P=0.016) and urinary PC ratio (P=0.007) in rats with HELLP. Blockade of the ET A receptor significantly decreased hemolysis (P=0.009), liver enzymes (P=0.006) and significantly increased platelet levels (P=0.03) in HELLP rats. These data support the hypothesis that ET‐1 activation has a critical role in pathophysiology of as HELLP syndrome. KW received IRSP support.