title: Abnormal uterine artery remodelling in the stroke prone spontaneously hypertensive rat.
abstract: BACKGROUND
  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 μm(2) vs. 95656 ± 8524 μm(2) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Electronic address: h.small.1@research.gla.ac.uk.
authors.forename: Heather Y
authors.initials: HY
authors.lastname: Small
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Morgan
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Beattie
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Sinead
authors.initials: S
authors.lastname: Griffin
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Marie
authors.initials: M
authors.lastname: Indahl
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Delles
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Delyth
authors.initials: D
authors.lastname: Graham
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D009543:Nifedipine / Q000627:therapeutic use; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D055988:Uterine Artery / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology
chemical_list: D000959:Antihypertensive Agents; D009543:Nifedipine
keywords: Hypertension; SHRSP; Uterine artery; Vascular remodelling