Brennan Lesley, Morton Jude S, Quon Anita, Davidge Sandra T
Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, T6G 2S2, Canada.
Women and Children's Health Research Institute, Edmonton, T6G 2R3, Canada.
PLoS One. 2016 Sep 22;11(9):e0162487. doi: 10.1371/journal.pone.0162487. eCollection 2016.
Preeclampsia is a disorder affecting 2-8% of all pregnancies, characterized by gestational hypertension (≥ 140/90 mmHg) and proteinuria (≥300 mg over 24 hours) diagnosed following the 20th week of pregnancy, and for which there is currently no available treatment. While the precise cause of preeclampsia is unknown, placental ischemia/hypoxia resulting from abnormal trophoblast invasion and maternal endothelial dysfunction are central characteristics. Preeclampsia is a major cause of both maternal and fetal morbidity and mortality in the perinatal period. In addition, women who have experienced preeclampsia are more likely to suffer cardiovascular disease later in life. The cause of this elevation in cardiovascular risk postpartum, however, is unknown. We hypothesize that there may be lasting vascular dysfunction following exposure to reduced uteroplacental perfusion during pregnancy that may contribute to increased cardiovascular risk postpartum. Using the rat reduced utero-placental perfusion pressure (RUPP) model of preeclampsia, blood pressure was assessed in dams at gestational day 20, one and three months postpartum. Mesenteric artery and aortic function were assessed using wire myography. We demonstrated hypertension and increased mesenteric artery responses to phenylephrine at gestational day 20, with the latter due to a decreased contribution of nitric oxide without any change in methylcholine-induced relaxation. At one month postpartum, we demonstrated a small but significant vasoconstrictive phenotype that was due to an underlying loss of basal nitric oxide contribution. At three months postpartum, endothelium-dependent relaxation of the aorta demonstrated sensitivity to oxLDL and mesenteric arteries demonstrated decreased nitric oxide bioavailability with impaired methylcholine-induced relaxation; indicative of an early development of endothelial dysfunction. In summary, we have demonstrated impaired vascular function following exposure to a RUPP pregnancy that continued into the postpartum period; suggesting that a pregnancy complicated by preeclampsia may predispose women to later life cardiovascular disease via ongoing vascular dysfunction.
子痫前期是一种影响2%至8%所有妊娠的疾病，其特征为妊娠高血压（≥140/90 mmHg）和蛋白尿（24小时内≥300 mg），在妊娠20周后诊断出来，目前尚无有效治疗方法。虽然子痫前期的确切病因尚不清楚，但滋养细胞侵袭异常和母体血管内皮功能障碍导致的胎盘缺血/缺氧是其主要特征。子痫前期是围产期母婴发病和死亡的主要原因。此外，经历过子痫前期的女性在以后的生活中患心血管疾病的可能性更大。然而，产后心血管风险升高的原因尚不清楚。我们假设，孕期子宫胎盘灌注减少后可能存在持续的血管功能障碍，这可能导致产后心血管风险增加。使用子痫前期大鼠子宫胎盘灌注压力降低（RUPP）模型，在妊娠第20天、产后1个月和3个月评估母鼠的血压。使用线肌描记法评估肠系膜动脉和主动脉功能。我们发现在妊娠第20天时存在高血压，肠系膜动脉对去氧肾上腺素的反应增强，后者是由于一氧化氮的作用降低，而乙酰甲胆碱诱导的舒张无变化。在产后1个月，我们发现了一种轻微但显著的血管收缩表型，这是由于基础一氧化氮作用的潜在丧失。在产后3个月，主动脉的内皮依赖性舒张对氧化型低密度脂蛋白敏感，肠系膜动脉的一氧化氮生物利用度降低，乙酰甲胆碱诱导的舒张受损；这表明内皮功能障碍的早期发展。总之，我们证明了暴露于RUPP妊娠后血管功能受损，并持续到产后；这表明子痫前期合并妊娠可能通过持续的血管功能障碍使女性在以后的生活中易患心血管疾病。
