Magee-Womens Research Institute, Pittsburgh, Pennsylvania.
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
Am J Physiol Regul Integr Comp Physiol. 2021 Sep 1;321(3):R364-R376. doi: 10.1152/ajpregu.00115.2020. Epub 2021 Jul 14.
Preeclampsia is a spontaneously occurring pregnancy complication diagnosed by new-onset hypertension and end-organ dysfunction with or without proteinuria. This pregnancy-specific syndrome contributes to maternal morbidity and mortality and can have detrimental effects on fetal outcomes. Preeclampsia is also linked to increased risk of maternal cardiovascular disease throughout life. Despite intense investigation of this disorder, few treatment options are available. The aim of this study was to investigate the potential therapeutic effects of maternal l-citrulline supplementation on pregnancy-specific vascular dysfunction in the male C57BL/6J × female C57BL/6J preeclampsia-like mouse model. l-Citrulline is a nonessential amino acid that is converted to l-arginine to promote smooth muscle and blood vessel relaxation and improve nitric oxide (NO)-mediated vascular function. To model a preeclampsia-like pregnancy, female C57BL/6J mice were mated to male mice, and a subset of dams was supplemented with l-citrulline throughout pregnancy. Blood pressure, systemic vascular glycocalyx, and ex vivo vascular function were investigated in late pregnancy, and postpartum at 6 and 10 mo of age. Main findings show that l-citrulline reduced blood pressure, increased vascular glycocalyx volume, and rescued ex-vivo vascular function at in this preeclampsia-like model. The vascular benefit of l-citrulline also extended postpartum, with improved vascular function and glycocalyx measures at 6 and 10 mo of age. l-Citrulline-mediated vascular improvements appear, in part, attributable to NO pathway signaling. Taken together, l-citrulline supplementation during pregnancy appears to have beneficial effects on maternal vascular health, which may have translational implications for improved maternal cardiovascular health.
子痫前期是一种自发发生的妊娠并发症，由新发生的高血压和终末器官功能障碍引起，伴有或不伴有蛋白尿。这种妊娠特有的综合征导致母体发病率和死亡率增加，并可能对胎儿结局产生不利影响。子痫前期也与一生中母亲患心血管疾病的风险增加有关。尽管对这种疾病进行了深入研究，但可用的治疗选择很少。本研究旨在探讨母体 l-瓜氨酸补充对雄性 C57BL/6J×雌性 C57BL/6J 子痫前期样小鼠模型中妊娠特异性血管功能障碍的潜在治疗效果。l-瓜氨酸是一种非必需氨基酸，可转化为 l-精氨酸，以促进平滑肌和血管松弛，改善一氧化氮（NO）介导的血管功能。为了模拟子痫前期样妊娠，雌性 C57BL/6J 小鼠与雄性小鼠交配，一部分孕鼠在整个孕期补充 l-瓜氨酸。在妊娠晚期和产后 6 和 10 月龄时，研究了血压、全身血管糖萼和离体血管功能。主要发现表明，l-瓜氨酸可降低血压、增加血管糖萼体积，并在该子痫前期样模型中恢复离体血管功能。l-瓜氨酸的血管益处也在产后延伸，产后 6 和 10 月龄时血管功能和糖萼测量得到改善。l-瓜氨酸介导的血管改善部分归因于 NO 途径信号。总之，妊娠期间补充 l-瓜氨酸似乎对母体血管健康有益，这可能对改善母体心血管健康具有转化意义。
