Ps-B03-9: Eplerenone Prevents Cardiac Fibrosis by Inhibiting Angiogenesis in Unilateral Urinary Obstruction Rats

Abstract

A subset of ANGII and SHAM animals received daily 1% w/v MgSO 4 drinking water from GD0.5 (n = 4/group; SHAM/ANGII+MgSO 4 ). Blood pressure, cardiac function, and uteroplacental blood flow were measured by tail-cuff plethysmography and Doppler ultrasound pre-pregnancy (PP) and at GD6.5, 12.5, and 18.5. Urine samples were collected by metabolic cage at PP, GD6.5, and GD18.5 for measurement of proteinuria. Fetal and placental measurements were collected at sacrifice. Results: ANGII shows features consistent with SPE in humans via decreased stroke volume and elevated blood pressure alongside decreased fetal and placental weights vs SHAM (****p < 0.0001, **p < 0.01, *p < 0.05). Additionally, ANGII resulted in significantly altered fluid homeostasis and proteinuria vs SHAM (****p < 0.0001, ***p < 0.001, **p < 0.01). ANGII+MgSO 4 showed a decrease in blood pressure vs ANGII (**p < 0.01). Treatment with MgSO 4 had no significant effect on cardiac function, though there was a trend towards improvement in delta cardiac output. Neither ANGII nor additional MgSO 4 altered indices of uteroplacental flow vs ANGII or SHAM. ANGII+MgSO 4 exhibited a significant reduction in proteinuria vs ANGII (*p < 0.05) as well as improvements in fluid homeostasis. Both fetal and placental weights were significantly reduced in ANGII+MgSO 4 vs SHAM (**p < 0.001) indicating a detrimental effect.Conclusions: These results suggest 1% w/v MgSO 4 may be beneficial as a preventative therapeutic in pregnancies affected by super-imposed pre-eclampsia for maternal but not fetal outcomes. Further work is needed to elucidate the effects of MgSO 4 in the context of hypertensive pregnancy.