Fushima Tomofumi, Sekimoto Akiyo, Oe Yuji, Sato Emiko, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki
Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai Japan; and.
Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Am J Physiol Renal Physiol. 2017 Feb 1;312(2):F366-F372. doi: 10.1152/ajprenal.00501.2016. Epub 2016 Dec 7.
Preeclampsia (PE) is pregnancy-induced hypertension with proteinuria that typically develops after 20 wk of gestation. Antihypertensives currently used for PE reduce blood pressure of PE mothers but do not prevent preterm delivery and do not alleviate fetal growth restriction (FGR) associated with PE. We have recently shown that the activation of the endothelin (ET) system exacerbates PE. However, ET receptor antagonists are teratogenic and not suitable for pregnant women. The vitamin B nicotinamide (Nam) inhibits vasoconstriction by ET and is generally considered safe and harmless to babies. Nam also alleviates oxidative stress, which exacerbates PE and FGR. The aim of the present study was to evaluate therapeutic effects of Nam on the PE-like phenotype using a reduced uterine perfusion pressure (RUPP) model in mice that we have recently developed. We bilaterally ligated uterine vessels of pregnant mice and administered Nam or water daily by gavage. Nam improved maternal hypertension, proteinuria, and glomerular endotheliosis in RUPP mice. Moreover, Nam prolonged pregnancies and improved survival and growth of the embryos in RUPP PE mice. In conclusion, Nam alleviates the PE-like phenotype and FGR in the murine RUPP model. Nam could help treat maternal hypertension and FGR in human PE.
子痫前期（PE）是妊娠诱发的高血压并伴有蛋白尿，通常在妊娠20周后发病。目前用于治疗PE的抗高血压药物可降低PE母亲的血压，但不能预防早产，也不能缓解与PE相关的胎儿生长受限（FGR）。我们最近发现内皮素（ET）系统的激活会加重PE。然而，ET受体拮抗剂具有致畸性，不适合孕妇使用。维生素B烟酰胺（Nam）可抑制ET引起的血管收缩，通常被认为对胎儿安全无害。Nam还可减轻氧化应激，氧化应激会加重PE和FGR。本研究的目的是使用我们最近建立的小鼠子宫灌注压降低（RUPP）模型，评估Nam对PE样表型的治疗效果。我们双侧结扎妊娠小鼠的子宫血管，并通过灌胃每日给予Nam或水。Nam改善了RUPP小鼠的母体高血压、蛋白尿和肾小球内皮病变。此外，Nam延长了RUPP PE小鼠的妊娠期，并改善了胚胎的存活和生长。总之，Nam可减轻小鼠RUPP模型中的PE样表型和FGR。Nam可能有助于治疗人类PE中的母体高血压和FGR。
