Abstract 416: Hypertension During Pregnancy is Associated with Cerebral Damage in an Animal Model of severe preeclampsia
HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome is a severe form of preeclampsia that is accompanied by hypertension, headaches, visual disturbances and cerebral infarctions during pregnancy. HELLP is associated with hypertension and elevations in TNF-α and IL-6, both of which have been shown to activate the endothelin-1 system (ET-1). The objective of the current study was to determine if hypertension in an animal model of HELLP is associated with cerebral impairment. On gestational day (GD) 12 miniosmotic pumps infusing sEndoglin and sFlt-1 (7 and 4.7ug/kg/day) were implanted into normal pregnant (NP) rats to induce HELLP. On GD18 carotid catheters were inserted into HELLP and NP rats and mean arterial pressure (MAP) was recorded on GD19 followed by brain collection. Myogenic tone was calculated from the middle cerebral artery; brain water content was measured to determine cerebral edema. Blood brain barrier (BBB) permeability was determined by exposing cerebral vessels from non-pregnant rats intraluminally to plasma from NP or HELLP rats. MAP increased from 92±2.6mmHg in NP rats (n=10) to 120.6±3.6mmHg in HELLP rats (n=11; p<0.01). HELLP rats had significant cerebral edema compared to NP rats (p=0.04). Myogenic tone in HELLP rats was significantly impaired (p<0.05) at pressures greater than or equal to 80mmHg compared to NP rats (n=2/group). Plasma from HELLP rats (n=6) significantly increased BBB permeability at 100mmHg compared to plasma from NP rats (n=5). Administration of an endothelinA (ETA) receptor antagonist (ABT-627, 5mg/kg on GD12-19), significantly decreased MAP in HELLP rats compared to untreated HELLP rats (97±5.3mmHg, n=5, p<0.01) and decreased cerebral edema to levels comparable to NP rats. Data from this study demonstrates that high MAP in HELLP rats is accompanied by cerebral edema, increased BBB permeability and impaired myogenic tone. Any of which could contribute to the neurologic complications that plague women with HELLP. Furthermore, as elevated ET-1 can damage the BBB and lead to cerebral damage we administered an ETA receptor antagonist which significantly decreased MAP and cerebral edema; future studies will determine if these changes are accompanied by improvement in myogenic tone and BBB permeability.
Author Disclosures: K. Wallace: C. Other Research Support (includes receipt of drugs, supplies, equipment or other in-kind support); Modest; ABT-627 was a gift from Abbott Laboratories. S. Tremble: None. M.R. Pabbidi: None. R. Morris: None. S. Spencer: None. M. Cipolla: None.
- © 2014 by American Heart Association, Inc.