Abnormal uterine artery remodelling in the stroke prone spontaneously hypertensive rat

Abstract

IntroductionThe 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.MethodsDoppler 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.ResultsSHRSP 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.DiscussionWe 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.

Role of Tumor Necrosis Factor-α and Natural Killer Cells in Uterine Artery Function and Pregnancy Outcome in the Stroke-Prone Spontaneously Hypertensive Rat

“… 35 We have previously hypothesized that deficient uteroplacental perfusion in SHRSP leads to the premature utilization of glycogen stores in the placenta. 13 In agreement, improvement of uteroplacental blood flow in etanercept-treated SHRSP restores the presence of placental glycogen cells at GD 18.…”

“…Most of the methods have been previously described by our group including the implantation of radiotelemetry probes, 23 Doppler ultrasound, 13 myography of the uterine arteries, 13 , 24 and periodic acid–Schiff stain of the placenta. 13 Full details are found in the online-only Data Supplement .…”

“…We have shown that the SHRSP presents with reduced litter size and increased loss of glycogen storage from the placenta associated with spontaneous deficient uterine artery remodeling and blood flow relative to the contrasting strain, Wistar–Kyoto (WKY), at gestational day (GD) 18. 13 …”

Modeling Superimposed Preeclampsia Using Ang II (Angiotensin II) Infusion in Pregnant Stroke-Prone Spontaneously Hypertensive Rats

“…Pregnant stroke prone spontaneously hypertensive (SHRSP) rats have constantly elevated blood pressure, compared to the normotensive Wistar Kyoto (WKY) strain, and are hypertensive throughout pregnancy. SHRSP rats also demonstrate aspects of PE; such as reduced uteroplacental blood flow and impaired uterine artery function in late pregnancy 23. These vascular changes have been found to be independent of pre-existing hypertension and are not observed in WKY pregnancy.…”

Polymerization-Incompetent Uromodulin in the Pregnant Stroke-Prone Spontaneously Hypertensive Rat

“…14 We hypothesized that the urinary peptidome would be altered in both a pregnancy-dependent and strain-dependent manner between the SHRSP and control WKY strain.…”