Modeling superimposed preeclampsia using Ang II (Angiotensin II) infusion in pregnant stroke-prone spontaneously hypertensive rats

Morgan, H. L., Butler, E., Ritchie, S., Herse, F., Dechend, R., Beattie, E., McBride, M. W. and Graham, D. (2018) Modeling superimposed preeclampsia using Ang II (Angiotensin II) infusion in pregnant stroke-prone spontaneously hypertensive rats. Hypertension, 72(1), pp. 208-218. (doi:10.1161/HYPERTENSIONAHA.118.10935) (PMID:29844145) (PMCID:PMC6012051)

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Abstract

Hypertensive disorders of pregnancy are the second leading cause of maternal deaths worldwide. Superimposed preeclampsia is an increasingly common problem and often associated with impaired placental perfusion. Understanding the underlying mechanisms and developing treatment options are crucial. The pregnant stroke-prone spontaneously hypertensive rat has impaired uteroplacental blood flow and abnormal uterine artery remodeling. We used Ang II (angiotensin II) infusion in pregnant stroke-prone spontaneously hypertensive rats to mimic the increased cardiovascular stress associated with superimposed preeclampsia and examine the impact on the maternal cardiovascular system and fetal development. Continuous infusion of Ang II at 500 or 1000 ng/kg per minute was administered from gestational day 10.5 until term. Radiotelemetry and echocardiography were used to monitor hemodynamic and cardiovascular changes, and urine was collected prepregnancy and throughout gestation. Uterine artery myography assessed uteroplacental vascular function and structure. Fetal measurements were made at gestational day 18.5, and placentas were collected for histological and gene expression analyses. The 1000 ng/kg per minute Ang II treatment significantly increased blood pressure (P<0.01), reduced cardiac output (P<0.05), and reduced diameter and increased stiffness of the uterine arteries (P<0.01) during pregnancy. The albumin:creatinine ratio was increased in both Ang II treatment groups (P<0.05; P<0.0001). The 1000 ng/kg per minute–treated fetuses were significantly smaller than vehicle treatment (P<0.001). Placental expression of Ang II receptors was increased in the junctional zone in 1000 ng/kg per minute Ang II–treated groups (P<0.05), with this zone showing depletion of glycogen content and structural abnormalities. Ang II infusion in pregnant stroke-prone spontaneously hypertensive rats mirrors hemodynamic, cardiac, and urinary profiles observed in preeclamptic women, with evidence of impaired fetal growth.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McBride, Dr Martin and Beattie, Mrs Elisabeth and Butler, Mrs Elaine and Graham, Dr Delyth and Morgan, Hannah
Authors: Morgan, H. L., Butler, E., Ritchie, S., Herse, F., Dechend, R., Beattie, E., McBride, M. W., and Graham, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Hypertension
Publisher:American Heart Association
ISSN:0194-911X
ISSN (Online):1524-4563
Published Online:01 July 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Hypertension 72(1): 208-218
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
580941MRC Doctoral Training Grant 2011-2015Mary Beth KneafseyMedical Research Council (MRC)MR/J50032X/1VPO VICE PRINCIPAL RESEARCH & ENTERPRISE
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES