How do the uterine radial arteries adapt to normal pregnancy?

Abstract

Introduction: In order to maintain a healthy pregnancy, successful vascular remodelling of the maternal circulation is necessary to accommodate the increased utero-placental blood flow. Inadequate uterine vascular remodelling restricts blood flow and nutrients to the placenta, and is commonly linked to pregnancy complications such as fetal growth restriction (FGR). Uterine radial arteries have recently been recognised as important regulators of blood flow in pregnancy, providing a rate-limiting resistance towards the end of the first trimester. However, there is insufficient knowledge of how radial arteries adapt to normal pregnancy, and what mechanism drive changes in these arteries to support their remodelling. Methods: Histological specimens of human radial arteries across the first half of pregnancy (n=18) and radial arteries from non-pregnant and pregnant rats (n=6/group) were digitally quantified for arterial diameter and wall thickness measurements. The localization and expression of receptors for paracrine factors known to have key roles in uterine vascular remodelling were investigated through immunohistochemistry and western blot analysis of rat radial arteries. Western blot analysis was further performed to determine the expression of endothelial nitric oxide synthase (eNOS), as suggested downstream pathway of radial artery remodelling. Results: Human radial arteries significantly increased in luminal diameter between 6-8 weeks of gestation (n=5 specimens) and 16-20 weeks of gestation (p=0.013, n=6 specimens). No significant differences in wall thickness were observed across the first half of pregnancy (p=0.0538, n=18 specimens) or when compared between gestational age groups (p>0.1). Rat radial arteries also significantly increased in luminal diameter between non-pregnant and pregnant animals (p=0.0003, n=6/group). No significant difference was observed in wall thickness between non-pregnant and pregnant rat radial arteries (p=0.069, n=6/group). The expression of paracrine receptors and eNOS did not substantially change between non-pregnant and pregnant rat radial arteries in immunohistochemistry and western blot analysis (p>0.3). Discussion: Human and rat radial arteries exhibit outward hypertrophic remodelling in pregnancy, confirming rats as an appropriate animal model. Similar expression levels of investigated receptors and eNOS in virgin and late-pregnant animals suggest that radial arteries may possess a spare capacity to pregnancy-induced remodelling. Paracrine effects may contribute more to functional rather than structural vascular adaptation to pregnancy.