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AT1-AA infusion during pregnancy impairs CBF autoregulation postpartum

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Item Type:Article
Title:AT1-AA infusion during pregnancy impairs CBF autoregulation postpartum
Creators Name:Campbell, N. and Strong, L. and Fang, X. and Border, J.J. and Herrock, O. and Turner, T. and Deer, E. and Amaral, L. and Dechend, R. and Roman, R.J. and LaMarca, B.
Abstract:Preeclampsia (PE), new-onset hypertension during pregnancy alongside organ dysfunction, is a leading cause of morbidity and mortality for the mother and fetus. PE women have activated B cells that produce agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA). AT1-AA impairs cerebral blood flow (CBF) autoregulation during pregnancy. Although AT1-AA often remains elevated up to 8 years postpartum, AT1-AA's effect on CBF autoregulation postpartum is unknown. This study examined whether elevated AT1-AA during pregnancy impairs CBF autoregulation postpartum and if this was augmented by infusion of AT1-AA postpartum. AT1-AA was infused into 12-week-old timed-pregnant Sprague Dawley rats beginning on gestational day 14. Uterine artery resistance index (UARI) was measured on gestational day 18 as a measure of endothelial dysfunction associated with PE. Dams were allowed to deliver. One group was given a second infusion of AT1-AA (50% perinatal dose mimicking levels observed in postpartum PE women) at 9 weeks postpartum. After postpartum week 10, mean arterial pressure (MAP) was measured in conscious rats and CBF autoregulation was measured by laser Doppler flowmetry. AT1-AA during pregnancy increased UARI (P<0.05). AT1-AA during pregnancy did not affect MAP postpartum but did impair CBF autoregulation postpartum. Infusion of AT1-AA postpartum significantly elevated blood pressure (P<0.01) but did not further impair CBF autoregulation. This study demonstrates that circulating AT1-AA during pregnancy causes impairment of CBF autoregulation well into the postpartum period indicating that elevated AT1-AA leads to long-term cerebrovascular consequences. Targeting AT1-AA may prevent cerebrovascular effects associated with PE during pregnancy and postpartum.
Keywords:Autoantibodies, Blood Pressure, Cerebral Blood Flow, Inflammation, Preeclampsia, Animals, Rats
Source:International Journal of Cerebrovascular Disease and Stroke
Publisher:Gavin Publishers
Page Range:154
Date:17 July 2023
Official Publication:https://doi.org/10.29011/2688-8734.100154
PubMed:View item in PubMed

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