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The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats

BACKGROUND: Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to these cerebral abnormalities are not clear. Several lines of evidence suggest th...

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Autores principales: Warrington, Junie P., Fan, Fan, Duncan, Jeremy, Cunningham, Mark W., LaMarca, Babette B., Dechend, Ralf, Wallukat, Gerd, Roman, Richard J., Drummond, Heather A., Granger, Joey P., Ryan, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907203/
https://www.ncbi.nlm.nih.gov/pubmed/31829239
http://dx.doi.org/10.1186/s13293-019-0275-1
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author Warrington, Junie P.
Fan, Fan
Duncan, Jeremy
Cunningham, Mark W.
LaMarca, Babette B.
Dechend, Ralf
Wallukat, Gerd
Roman, Richard J.
Drummond, Heather A.
Granger, Joey P.
Ryan, Michael J.
author_facet Warrington, Junie P.
Fan, Fan
Duncan, Jeremy
Cunningham, Mark W.
LaMarca, Babette B.
Dechend, Ralf
Wallukat, Gerd
Roman, Richard J.
Drummond, Heather A.
Granger, Joey P.
Ryan, Michael J.
author_sort Warrington, Junie P.
collection PubMed
description BACKGROUND: Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to these cerebral abnormalities are not clear. Several lines of evidence suggest that angiotensin II can impact cerebrovascular function; however, the role of the renin angiotensin system in cerebrovascular function during placental ischemia has not been examined. We tested whether the angiotensin type 1 (AT1) receptor contributes to impaired CBF autoregulation in pregnant rats with placental ischemia caused by surgically reducing uterine perfusion pressure. METHODS: Placental ischemic or sham operated rats were treated with vehicle or losartan from gestational day (GD) 14 to 19 in the drinking water. On GD 19, we assessed CBF autoregulation in anesthetized rats using laser Doppler flowmetry. RESULTS: Placental ischemic rats had impaired CBF autoregulation that was attenuated by treatment with losartan. In addition, we examined whether an agonistic autoantibody to the AT1 receptor (AT1-AA), reported to be present in preeclamptic women, contributes to impaired CBF autoregulation. Purified rat AT1-AA or vehicle was infused into pregnant rats from GD 12 to 19 via mini-osmotic pumps after which CBF autoregulation was assessed. AT1-AA infusion impaired CBF autoregulation but did not affect brain water content. CONCLUSIONS: These results suggest that the impaired CBF autoregulation associated with placental ischemia is due, at least in part, to activation of the AT1 receptor and that the RAS may interact with other placental factors to promote cerebrovascular changes common to preeclampsia.
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spelling pubmed-69072032019-12-20 The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats Warrington, Junie P. Fan, Fan Duncan, Jeremy Cunningham, Mark W. LaMarca, Babette B. Dechend, Ralf Wallukat, Gerd Roman, Richard J. Drummond, Heather A. Granger, Joey P. Ryan, Michael J. Biol Sex Differ Research BACKGROUND: Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to these cerebral abnormalities are not clear. Several lines of evidence suggest that angiotensin II can impact cerebrovascular function; however, the role of the renin angiotensin system in cerebrovascular function during placental ischemia has not been examined. We tested whether the angiotensin type 1 (AT1) receptor contributes to impaired CBF autoregulation in pregnant rats with placental ischemia caused by surgically reducing uterine perfusion pressure. METHODS: Placental ischemic or sham operated rats were treated with vehicle or losartan from gestational day (GD) 14 to 19 in the drinking water. On GD 19, we assessed CBF autoregulation in anesthetized rats using laser Doppler flowmetry. RESULTS: Placental ischemic rats had impaired CBF autoregulation that was attenuated by treatment with losartan. In addition, we examined whether an agonistic autoantibody to the AT1 receptor (AT1-AA), reported to be present in preeclamptic women, contributes to impaired CBF autoregulation. Purified rat AT1-AA or vehicle was infused into pregnant rats from GD 12 to 19 via mini-osmotic pumps after which CBF autoregulation was assessed. AT1-AA infusion impaired CBF autoregulation but did not affect brain water content. CONCLUSIONS: These results suggest that the impaired CBF autoregulation associated with placental ischemia is due, at least in part, to activation of the AT1 receptor and that the RAS may interact with other placental factors to promote cerebrovascular changes common to preeclampsia. BioMed Central 2019-12-11 /pmc/articles/PMC6907203/ /pubmed/31829239 http://dx.doi.org/10.1186/s13293-019-0275-1 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Warrington, Junie P.
Fan, Fan
Duncan, Jeremy
Cunningham, Mark W.
LaMarca, Babette B.
Dechend, Ralf
Wallukat, Gerd
Roman, Richard J.
Drummond, Heather A.
Granger, Joey P.
Ryan, Michael J.
The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats
title The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats
title_full The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats
title_fullStr The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats
title_full_unstemmed The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats
title_short The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats
title_sort angiotensin ii type i receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907203/
https://www.ncbi.nlm.nih.gov/pubmed/31829239
http://dx.doi.org/10.1186/s13293-019-0275-1
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