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 B3 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.