Abnormal uterine artery remodelling in the stroke prone spontaneously hypertensive rat

Small, H. Y., Morgan, H., Beattie, E., Griffin, S., Indahl, M., Delles, C. and Graham, D. (2016) Abnormal uterine artery remodelling in the stroke prone spontaneously hypertensive rat. Placenta, 37, pp. 34-44. (doi:10.1016/j.placenta.2015.10.022) (PMID:26612342) (PMCID:PMC4721537)

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Abstract

Introduction: The stroke prone spontaneously hypertensive rat (SHRSP) is an established model of human cardiovascular risk. We sought to characterise the uteroplacental vascular response to pregnancy in this model and determine whether this is affected by the pre-existing maternal hypertension. Methods: Doppler ultrasound and myography were utilised to assess uterine artery functional and structural changes pre-pregnancy and at gestational day 18 in SHRSP (untreated and nifedipine treated) and in the normotensive Wistar-Kyoto (WKY) rat. Maternal adaptations to pregnancy were also assessed along with histology and expression of genes involved in oxidative stress in the placenta. Results: SHRSP uterine arteries had a pulsatile blood flow and were significantly smaller (70906 ± 3903 μm2 vs. 95656 ± 8524 μm2 cross-sectional area; p<0.01), had a significant increase in contractile response (57.3 ± 10.5 kPa vs 27.7 ± 1.9 kPa; p<0.01) and exhibited impaired endothelium-dependent vasorelaxation (58.0 ± 5.9 % vs 13.9 ± 4.6 %; p<0.01) compared to WKY. Despite significant blood pressure lowering, nifedipine did not improve uterine artery remodelling, function or blood flow in SHRSP. Maternal plasma sFLT-1/PlGF ratio (5.3 ± 0.3 vs 4.6 ± 0.1; p<0.01) and the urinary albumin/creatinine ratio (1.9 ± 0.2 vs 0.6 ± 0.1; p<0.01) was increased in SHRSP vs WKY. The SHRSP placenta had a significant reduction in glycogen cell content and an increase in Hif1α, Sod1 and Vegf. Discussion: We conclude that the SHRSP exhibits a number of promising characteristics as a model of spontaneous deficient uteroplacental remodelling that adversely affect pregnancy outcome, independent of pre-existing hypertension.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Graham, Dr Delyth and Morgan, Miss Hannah and Delles, Professor Christian and Beattie, Mrs Elisabeth
Authors: Small, H. Y., Morgan, H., Beattie, E., Griffin, S., Indahl, M., Delles, C., and Graham, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Placenta
Publisher:Elsevier B.V.
ISSN:0143-4004
ISSN (Online):1532-3102
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Placenta 37:34-44
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/1VICE PRINCIPAL RESEARCH & ENTERPRISE
492454BHF 4 Year PhD ProgrammeAnna DominiczakBritish Heart Foundation (BHF)FS/12/66/30003RI CARDIOVASCULAR & MEDICAL SCIENCES