Marshall Sarah A, Senadheera Sevvandi N, Jelinic Maria, O'Sullivan Kelly, Parry Laura J, Tare Marianne
School of BioSciences, The University of Melbourne, Parkville, VIC, Australia.
Department of Physiology and Monash Rural Health, Monash University, Melbourne, VIC, Australia.
Front Physiol. 2018 Mar 22;9:255. doi: 10.3389/fphys.2018.00255. eCollection 2018.
The uterine vasculature undergoes profound adaptations in response to pregnancy. Augmentation of endothelial vasodilator function and reduced smooth muscle reactivity are factors contributing to uterine artery adaptation and are critical for adequate placental perfusion. The peptide hormone relaxin has an important role in mediating the normal maternal renal vascular adaptations during pregnancy through a reduction in myogenic tone and an increase in flow-mediated vasodilation. Little is known however about the influence of endogenous relaxin on the uterine artery during pregnancy. We tested the hypothesis that relaxin deficiency increases myogenic tone and impairs endothelial vasodilator function in uterine arteries of late pregnant relaxin deficient () mice. Reactivity of main uterine arteries from non-pregnant and late pregnant wild-type () and mice was studied using pressure and wire myography and changes in gene expression explored using PCR. Myogenic tone was indistinguishable in arteries from non-pregnant mice. In late pregnancy uterine artery myogenic tone was halved in mice ( < 0.0001), an adaptation that failed to occur in arteries from pregnant mice. The role of vasodilator prostanoids in the regulation of myogenic tone was significantly reduced in arteries of pregnant mice ( = 0.02). Agonist-mediated endothelium-dependent vasodilation was significantly impaired in non-pregnant mice. With pregnancy, differences in total endothelial vasodilator function were resolved, although there remained an underlying deficiency in the role of vasodilator prostanoids and alterations to the contributions of calcium-activated K channels. Fetuses of late pregnant mice were ~10% lighter ( < 0.001) than those of mice. In conclusion, relaxin deficiency is associated with failed suppression of uterine artery myogenic tone in pregnancy, which likely contributes to reduced uteroplacental perfusion and fetal growth restriction.
子宫血管系统会因妊娠而发生深刻的适应性变化。内皮舒张功能增强和平滑肌反应性降低是促成子宫动脉适应性变化的因素，对胎盘的充分灌注至关重要。肽类激素松弛素在介导孕期母体正常的肾血管适应性变化中发挥重要作用，其作用机制是降低肌源性张力并增加血流介导的血管舒张。然而，关于内源性松弛素在孕期对子宫动脉的影响，人们了解甚少。我们检验了这样一个假设：松弛素缺乏会增加晚期妊娠的松弛素缺乏（）小鼠子宫动脉的肌源性张力，并损害其内皮舒张功能。使用压力和线肌动描记法研究了非妊娠和晚期妊娠野生型（）及小鼠子宫主动脉的反应性，并使用聚合酶链反应探索了基因表达的变化。非妊娠小鼠动脉的肌源性张力没有差异。在晚期妊娠时，小鼠子宫动脉的肌源性张力减半（<0.0001），而妊娠小鼠的动脉未出现这种适应性变化。在妊娠小鼠的动脉中，血管舒张性前列腺素在调节肌源性张力中的作用显著降低（=0.02）。在非妊娠小鼠中，激动剂介导的内皮依赖性血管舒张明显受损。随着妊娠的进展，尽管血管舒张性前列腺素的作用仍存在潜在缺陷，且钙激活钾通道的贡献也发生了改变，但总内皮舒张功能的差异得到了解决。晚期妊娠小鼠的胎儿比小鼠的胎儿轻约10%（<0.001）。总之，松弛素缺乏与孕期子宫动脉肌源性张力抑制失败有关，这可能导致子宫胎盘灌注减少和胎儿生长受限。
