Abstract P205: G Protein-Coupled Estrogen Receptor Stimulation Attenuates Hypertension And Cardiac Dysfunction In The Reduced Uterine Perfusion Pressure Model Of Preeclampsia

Abstract

Preeclampsia (PE) is a disorder of pregnancy associated with maternal hypertension and cardiac dysfunction. Women with a history of PE have increased risk of cardiovascular disease and mortality that persist well beyond the post-partum period. Evidence suggests that the new estrogen receptor (GPER) is a beneficial regulator of placental development. Other studies have shown the role of GPER in promoting vasodilation and cardioprotection. However, the cardiovascular effects of GPER in an animal model of PE have not yet been determined. Thus, we hypothesize that the activation of GPER by its selective agonist G-1 is associated with the regulation of hypertension and cardiac dysfunction in rats following placental insufficiency. The reduced uterine perfusion pressure (RUPP) model was used to induce placental insufficiency in the dam by placing silver clips on abdominal aorta and uterine arteries on gestational day (GD) 14 of a 19-day gestation. RUPP rats received G-1 (100 μg/kg/day) or vehicle subcutaneously by osmotic minipump. Echocardiography was performed on GD18 to assess the effectiveness of G-1 on heart function in PE dams. On GD19, rats had carotid catheters placed, and hemodynamic measurements were made. RUPP rats exhibited hypertension and cardiac alterations, including global myocardial motion dyssynchrony, and reduced left ventricular systolic and diastolic function when compared with SHAM animals. G-1 treatment significantly attenuated hypertension and cardiac functional aberrations caused by PE in RUPP rats, a finding that may have important implications for the ongoing clinical evaluations of new drugs for the treatment of PE and its comorbidities.