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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., Strong, L., Fang, X., Border, J.J., Herrock, O., Turner, T., Deer, E., Amaral, L., Dechend, R., 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
ISSN:2688-8734
Publisher:Gavin Publishers
Volume:6
Number:1
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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