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 W. Cunningham

doi:10.1080/10641955.2020.1833215

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 W. Cunningham

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English (US)
Pages (from-to)	451-460
Number of pages	10
Journal	Hypertension in Pregnancy
Volume	39
Issue number	4
DOIs	https://doi.org/10.1080/10641955.2020.1833215
State	Published - Nov 2020
Externally published	Yes

Keywords

AT1-AA
BBB Permeability
CBF autoregulation
Preeclampsia
hypertension
placental ischemia

ASJC Scopus subject areas

Internal Medicine
Obstetrics and Gynecology

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10.1080/10641955.2020.1833215

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Duncan, J. W., Azubuike, D., Booz, G. W., Fisher, B., Williams, J. M., Fan, F., Ibrahim, T., LaMarca, B., & Cunningham, M. W. (2020). Angiotensin II type 1 receptor autoantibody blockade improves cerebral blood flow autoregulation and hypertension in a preclinical model of preeclampsia. Hypertension in Pregnancy, 39(4), 451-460. https://doi.org/10.1080/10641955.2020.1833215

Duncan, JW, Azubuike, D, Booz, GW, Fisher, B, Williams, JM, Fan, F, Ibrahim, T, LaMarca, B & Cunningham, MW 2020, 'Angiotensin II type 1 receptor autoantibody blockade improves cerebral blood flow autoregulation and hypertension in a preclinical model of preeclampsia', Hypertension in Pregnancy, vol. 39, no. 4, pp. 451-460. https://doi.org/10.1080/10641955.2020.1833215

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title = "Angiotensin II type 1 receptor autoantibody blockade improves cerebral blood flow autoregulation and hypertension in a preclinical model of preeclampsia",

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 ({\textquoteleft}n7AAc{\textquoteright}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:{\textquoteleft}n7AAc{\textquoteright} 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.",

keywords = "AT1-AA, BBB Permeability, CBF autoregulation, Preeclampsia, hypertension, placental ischemia",

author = "Duncan, {Jeremy W.} and Daniel Azubuike and Booz, {George W.} and Brandon Fisher and Williams, {Jan M.} and Fan Fan and Tarek Ibrahim and Babbette LaMarca and Cunningham, {Mark W.}",

note = "Publisher Copyright: {\textcopyright} 2020 Informa UK Limited, trading as Taylor & Francis Group.",

year = "2020",

month = nov,

doi = "10.1080/10641955.2020.1833215",

language = "English (US)",

volume = "39",

pages = "451--460",

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AU - Duncan, Jeremy W.

AU - Azubuike, Daniel

AU - Booz, George W.

AU - Fisher, Brandon

AU - Williams, Jan M.

AU - Fan, Fan

AU - Ibrahim, Tarek

AU - LaMarca, Babbette

AU - Cunningham, Mark W.

PY - 2020/11

Y1 - 2020/11

N2 - 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.

AB - 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.

KW - AT1-AA

KW - BBB Permeability

KW - CBF autoregulation

KW - Preeclampsia

KW - hypertension

KW - placental ischemia

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Angiotensin II type 1 receptor autoantibody blockade improves cerebral blood flow autoregulation and hypertension in a preclinical model of preeclampsia

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