61 Nicotinamide ameliorates PE and FGR in a mouse model of PE

Abstract

Introduction We have reported that lack of eNOS exacerbated preeclampsia (PE) via activation of endothelin (ET) system (Li, Takahashi et al. J Am Soc Nephrol, 2012). But inhibiting ET system is teratogenic, and is not suitable for pregnant women. Nicotinamide, a non-taratogenic vitamin, inhibits ADP ribosyl cyclase and relaxes vasculatures preconstricted with ET-1. Objectives The purpose of this study is to clarify whether nicotinamide is useful for treating or preventing PE and fetal growth restriction (FGR) associated with it. Methods Recombinant adenovirus to overproduce sFlt-1 was administered to ICR mice on 14.5 dpc to make a PE model. Changes in maternal body weight and BP were monitored. Dams were sacrificed on 18.5 dpc for further analysis. Results BP of the PE mice was significantly increased, PE dams miscarried, and fetal body weights were significantly decreased. Nicotinamide decreased BP of the dams by inhibiting ADP ribosyl cyclase, and prolonged pregnancy. Acting via NAD salvage pathway, nicotinamide normalized fetal ATP synthesis and prevented FGR. Conclusions Because nicotinamide benefits both mothers and pups, it merits evaluation for preventing and treating PE and FGR associated with it in humans.