Angiotensin II type 1 receptor autoantibody blockade improves cerebral blood flow autoregulation and hypertension in a preclinical model of preeclampsia
Jeremy W. Duncan, Daniel Azubuike, George W. Booz, Brandon Fisher, Jan M. Williams, Fan Fan, Tarek Ibrahim, Babbette LaMarca, Mark Cunningham
Abstract
Introduction:Women with preeclampsia (PE) and reduced uterine perfusion pressure (RUPP) pre-clinical rat model of PE have elevated angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA) and cerebrovascular dysfunction.Methods:Sprague Dawley rats had RUPP surgery with/without AT1-AA inhibitor (‘n7AAc’144 μg/day) osmotic minipumps. Mean arterial pressure (MAP), CBF autoregulation, blood brain barrier (BBB) permeability, cerebral edema, oxidative stress, and eNOS were assessed.Results:‘n7AAc’ improved MAP, restored CBF autoregulation, prevented cerebral edema, elevated oxidative stress, and increased phosphorylated eNOS protein in RUPP rats.Conclusion:Inhibiting the AT1-AA in placental ischemic rats prevents hypertension, cerebrovascular dysfunction, and improves cerebral metabolic function.