title: Nicotinamide ameliorates a preeclampsia-like condition in mice with reduced uterine perfusion pressure.
abstract: 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 B3nicotinamide (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.
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai Japan; and.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Fushima
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai Japan; and.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Sekimoto
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oe
authors.affiliation: 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.
authors.forename: Emiko
authors.initials: E
authors.lastname: Sato
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
authors.affiliation: 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.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai Japan; and ntakaha@m.tohoku.ac.jp.|Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005317:Fetal Growth Retardation / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D009536:Niacinamide / Q000494:pharmacology / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011507:Proteinuria / Q000188:drug therapy* / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects; D016896:Treatment Outcome; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D009536:Niacinamide
keywords: fetal growth restriction; glomerular endotheliosis; hypertension; hypoxia