Abstract 575: Complement Activation in Placental Ischemia-induced Hypertension is not dependent on Angiotensin II Type 1 Receptor

Abstract

Early onset preeclampsia is characterized by hypertension, reduced placental perfusion, intrauterine growth restriction and increased activation of complement, part of innate immunity. We reported that inhibition of complement activation attenuated reduced uterine perfusion pressure (RUPP)-induced hypertension in the pregnant rat. Although recent studies in pregnant mice indicate injection of autoantibodies to angiotensin II Type 1 receptor (AT1-AA) activate complement and increase blood pressure, the sequence of events following placental ischemia remains unknown. Thus, we hypothesized AT1-AA interaction with its antigen was responsible for complement activation critical to placental ischemia-induced hypertension. The AT1 antagonist losartan prevents AT1-AA interaction with the AT1 receptor. Thus, we determined the effect of losartan on complement activation following placental ischemia in rat. Dams received drinking water with or without 30 mg/kg/day losartan on gestation day (GD)13-19. On GD14, rats underwent Sham surgery or RUPP surgery with placement of clips on abdominal aorta and uterine arteries to decrease placental perfusion. On GD19, mean arterial pressure (MAP) via arterial catheter and serum C3a as an indicator of complement activation were measured. As expected, RUPP surgery increased complement activation (C3a) and MAP and decreased fetal weight compared to Sham. Importantly, losartan treatment did not significantly change RUPP-induced increase in C3a. These data indicate AT1-AA interaction with the AT1 receptor does not mediate complement activation and its subsequent involvement in hypertension following placental ischemia.