[87-OR]: Hypertension in an animal model of HELLP syndrome proceeds via activation of the Endothelin-1 system

Objectives We have shown that infusion of sFlt-1 and sEndoglin into normal pregnant rats causes Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP). Additionally these animals have hypertension, elevated TNF α , IL-6 and increased CD4 + T cells, all of which have been shown to activate the endothelin-1 system (ET-1) and are elevated in women with HELLP. Objective : To test thehypothesis that hypertension in response to HELLP was associated with ET-1 activation. Methods sFlt-1 and sEndoglin (4.7; 7 μg/kg/day respectively) were infused via mini-osmotic pump into normal pregnant rats (NP) on gestational day (GD) 12 to create HELLP. On GD 18 arterial catheters were inserted and on GD 19, Mean Arterial Pressure (MAP) was analyzed in HELLP and NP rats; serum, urine and tissues were collected for molecular analysis. Results When compared to NP, rats with HELLP had significantly increased lactate dehydrogenase (463 ± 48 vs. 630 ± 47.4 IU/L; P P 6  ± 3.2 × 10 5 vs. 3 × 10 6  ± 4.8 × 10 5  μL; P P P P P A receptor antagonist (ABT-627, 5 mg/kg) via drinking water. ET A receptor antagonism prevented hypertension in HELLP compared to NP (91.8 ± 4.3 vs. 91.5 ± 3.6 mmHg) rats. There was also an increase in platelet levels in treated HELLP rats compared to untreated HELLP (528,714 μL vs. 299,500 μL; P A receptor antagonism. Conclusions These data support the hypothesis that hypertension in response to HELLP proceeds via activation of the ET-1 system. Disclosures R. Morris: None. S. Spencer: None. K. Chatman: None. P. Kyle: None. J. Moseley: None. K. Wallace: None.