Eplerenone lowers maternal blood pressure in a model of leptin-induced preeclampsia, but decreases fetal growth when administered mid-, but not late-, gestation

Preeclampsia induces adverse cardiovascular outcomes for both mother and offspring. We established a novel leptin-induced mouse model of preeclampsia that induces hypertension, endothelial dysfunction, and fetal growth restriction, which are collectively ablated by endothelial cell mineralocorticoid receptor (MR) deletion. However, literature lacks preclinical evidence to use MR antagonism for preeclamptic patients. We hypothesize eplerenone improves blood pressure, vascular function, and fetal outcomes in leptin-infused pregnant mice. We infused timed-pregnant Balb/c mice with saline (sham) or leptin via s.c. osmotic minipump and administered vehicle or eplerenone from gestation day (GD)11-18 and GD15-18. We measured mean arterial blood pressure (BP) via radiotelemetry, vascular function in 2 nd order mesenteric arteries by wire myography, and pup/placental weights on GD18. Eplerenone from GD11-18 ablated leptin-induced increases in BP but independently decreased fetal weight and placental efficiency. Eplerenone increased vascular contractility to phenylephrine and increased mRNA expression of NADPH oxidase (NOX) 1 and 2 in the placentas of pregnant mice in the GD11-18 cohort. We observed in our GD15-18 cohort that eplerenone no longer decreased fetal weight nor placental efficiency and there was no increase in contractility to phenylephrine. In conclusion, our data suggest that although eplerenone improves leptin-induced hypertension in pregnant mice, eplerenone reduces fetal weight when administered at mid-, but not late-, gestation in pregnant mice.