Abstract 091: Chronic Vasopressin Infusion: A Novel, Clinically Significant, and Pregnancy-Specific Mouse Model of Preeclampsia

Recently we demonstrated that the late-pregnancy cardiovascular disorder, preeclampsia, is characterized by robust, early and sustained vasopressin (AVP) hypersecretion in all three trimesters of pregnancy in humans. We hypothesize a causative role for elevated AVP in the pathogenesis of preeclampsia. This concept was tested by chronically infusing AVP (0.24 - 240 ng/hr, s.c., or saline vehicle) in wildtype C57BL/6J female mice throughout pregnancy. In pregnant mice, AVP infusion caused pregnancy-specific increases in systolic blood pressure by tail-cuff plethysmography with significant increases in the pregnant cohort (saline n=16: 110±3, vs 24 ng/hr AVP n=11: 120±3 mmHg on GD15/16, P0.05). In addition, the AVP infused mice exhibited increased proteinuria (0.24 ng/hr n=2: 66±73, 2.4 ng/hr n=5: 348±56, 24 ng/hr n=2: 799±297 mg/d, Ppregnancy-specific physiological model of preeclampsia in mice. These data support our hypothesis that AVP hypersecretion during pregnancy may be causative for the development of preeclampsia. Ongoing experiments are aimed at identifying the causes of AVP hypersecretion in human preeclampsia, the target tissues and receptors involved, and the utility of targeting AVP signaling as a novel therapeutic for preeclampsia.