Department of Obstetrics and Gynaecology, Therapeutics Discovery and Vascular Function Group, The University of Melbourne and Mercy Hospital for Women, Heidelberg, Australia
Mercy Perinatal, Heidelberg, Australia.
Life Sci Alliance. 2022 Aug 5;5(12):e202201517. doi: 10.26508/lsa.202201517.
Preeclampsia affects ∼2-8% of pregnancies worldwide. It is associated with increased long-term maternal cardiovascular disease risk. This study assesses the effect of the vasoconstrictor N(ω)-nitro-L-arginine methyl ester (L-NAME) in modelling preeclampsia in mice, and its long-term effects on maternal cardiovascular health. In this study, we found that L-NAME administration mimicked key characteristics of preeclampsia, including elevated blood pressure, impaired fetal and placental growth, and increased circulating endothelin-1 (vasoconstrictor), soluble fms-like tyrosine kinase-1 (anti-angiogenic factor), and C-reactive protein (inflammatory marker). Post-delivery, mice that received L-NAME in pregnancy recovered, with no discernible changes in measured cardiovascular indices at 1-, 2-, and 4-wk post-delivery, compared with matched controls. At 10-wk post-delivery, arteries collected from the L-NAME mice constricted significantly more to phenylephrine than controls. In addition, these mice had increased kidney and heart mRNA expression, indicating increased inflammation. These findings suggest that though administration of L-NAME in mice certainly models key characteristics of preeclampsia during pregnancy, it does not appear to model the adverse increase in cardiovascular disease risk seen in individuals after preeclampsia.
先兆子痫影响全球 2-8%的妊娠。它与增加的长期母亲心血管疾病风险有关。本研究评估了血管收缩剂 N(ω)-硝基-L-精氨酸甲酯 (L-NAME) 在模拟小鼠先兆子痫中的作用及其对母体心血管健康的长期影响。在这项研究中,我们发现 L-NAME 给药模拟了先兆子痫的关键特征,包括血压升高、胎儿和胎盘生长受损以及循环内皮素-1(血管收缩剂)、可溶性 fms 样酪氨酸激酶-1(抗血管生成因子)和 C 反应蛋白(炎症标志物)增加。分娩后,接受 L-NAME 治疗的小鼠在怀孕期间恢复,与匹配的对照组相比,分娩后 1、2 和 4 周时测量的心血管指数没有明显变化。分娩后 10 周,来自 L-NAME 小鼠的动脉对苯肾上腺素的收缩明显大于对照组。此外,这些小鼠的肾脏和心脏 mRNA 表达增加,表明炎症增加。这些发现表明,尽管在小鼠中给予 L-NAME 肯定会在怀孕期间模拟先兆子痫的关键特征,但它似乎不会模拟先兆子痫后个体心血管疾病风险增加的不良情况。