AT1-AA Infusion during Pregnancy Impairs CBF Autoregulation Postpartum.
Autoantibodies
Blood pressure
Cerebral blood flow
Inflammation
Preeclampsia
Journal
International journal of cerebrovascular disease and stroke
Titre abrégé: Int J Cerebrovasc Dis Stroke
Pays: United States
ID NLM: 101740388
Informations de publication
Date de publication:
2023
2023
Historique:
medline:
30
10
2023
pubmed:
30
10
2023
entrez:
30
10
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37901747
doi: 10.29011/2688-8734.100154
pmc: PMC10610033
mid: NIHMS1930133
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NICHD NIH HHS
ID : F31 HD110230
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG079336
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD067541
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL138685
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM121334
Pays : United States
Déclaration de conflit d'intérêts
Conflict of Interest Statement The authors report no conflict of interest.
Références
Rev Physiol Biochem Pharmacol. 1984;101:161-211
pubmed: 6441228
Hypertension. 2018 May;71(5):886-893
pubmed: 29555668
Biol Sex Differ. 2021 Nov 2;12(1):58
pubmed: 34727994
Midwifery. 2015 Dec;31(12):1127-34
pubmed: 26460274
Hypertension. 2010 May;55(5):1246-53
pubmed: 20351341
Brain Behav Immun. 2022 Mar;101:93-135
pubmed: 34973396
J Autoimmun. 2021 Aug;122:102683
pubmed: 34144328
EClinicalMedicine. 2021 Aug;38:101019
pubmed: 34308300
Am J Physiol. 1978 Apr;234(4):H371-83
pubmed: 645875
Nature. 2021 Jul;595(7866):283-288
pubmed: 34010947
Hypertension. 2007 Mar;49(3):612-7
pubmed: 17210828
Geroscience. 2020 Oct;42(5):1387-1410
pubmed: 32696219
Biol Sex Differ. 2019 Dec 11;10(1):58
pubmed: 31829239
J Clin Med. 2021 Aug 19;10(16):
pubmed: 34441971
Am J Physiol Regul Integr Comp Physiol. 2017 Jan 1;312(1):R125-R131
pubmed: 27903510
Am J Obstet Gynecol. 2022 Feb;226(2S):S1237-S1253
pubmed: 32980358
Obstet Gynecol. 2019 Jan;133(1):1
pubmed: 30575675
Am J Physiol Renal Physiol. 2016 Dec 1;311(6):F1125-F1134
pubmed: 27707703
Hypertension. 2008 Dec;52(6):1168-72
pubmed: 18852381
J Transl Autoimmun. 2021;4:100100
pubmed: 33880442
Hypertension. 2019 Jul;74(1):5-13
pubmed: 31055951
Arch Intern Med. 1992 May;152(5):938-45
pubmed: 1580719
J Clin Invest. 1999 Apr;103(7):945-52
pubmed: 10194466
Am J Physiol Regul Integr Comp Physiol. 2022 Nov 1;323(5):R670-R681
pubmed: 36121142
Hypertens Pregnancy. 2020 Nov;39(4):451-460
pubmed: 33119997
Science. 2020 Oct 23;370(6515):
pubmed: 32972996
Am J Physiol Heart Circ Physiol. 2021 Feb 1;320(2):H535-H548
pubmed: 33275518
Semin Perinatol. 2009 Jun;33(3):130-7
pubmed: 19464502
BMJ. 2018 Oct 17;363:k4109
pubmed: 30333106
Front Immunol. 2022 Sep 27;13:981532
pubmed: 36238301
Obstet Gynecol. 2001 Apr;97(4):533-8
pubmed: 11275024
J Clin Invest. 1973 Nov;52(11):2682-9
pubmed: 4355997
Acta Neuropathol. 1970;16(2):117-24
pubmed: 4097399
Am J Physiol. 1981 Apr;240(4):H511-27
pubmed: 7223903
Hypertension. 2009 Oct;54(4):905-9
pubmed: 19704104
Obstet Gynecol. 2013 Nov;122(5):1064-1069
pubmed: 24104783
Gend Med. 2011 Jun;8(3):184-8
pubmed: 21600854
Sci Transl Med. 2020 Nov 18;12(570):
pubmed: 33139519
J Reprod Immunol. 2018 Aug;128:23-29
pubmed: 29843114
Pregnancy Hypertens. 2019 Jan;15:72-77
pubmed: 30825931
Hypertension. 2013 Nov;62(5):886-92
pubmed: 24041954
Hypertension. 2018 Jul;72(1):24-43
pubmed: 29899139
Stroke. 1989 Jan;20(1):45-52
pubmed: 2492126
Am J Physiol Heart Circ Physiol. 2022 Feb 1;322(2):H246-H259
pubmed: 34951541
N Engl J Med. 2005 Feb 10;352(6):558-69
pubmed: 15703421
Cardiovasc Toxicol. 2014 Mar;14(1):21-9
pubmed: 24122090
PLoS One. 2013 Nov 21;8(11):e80709
pubmed: 24278308
Int J Mol Sci. 2014 Jun 27;15(7):11495-509
pubmed: 24979132
Am J Obstet Gynecol MFM. 2021 Jan;3(1):100275
pubmed: 33451592
Nat Med. 2013 Dec;19(12):1584-96
pubmed: 24309662
Am J Hypertens. 2011 Jul;24(7):835-40
pubmed: 21472019
Hypertension. 2016 Nov;68(5):1308-1313
pubmed: 27698062
Am J Hypertens. 2010 Aug;23(8):911-6
pubmed: 20431529
Ann Biomed Eng. 1985;13(3-4):303-10
pubmed: 3898928