Abstract
Introduction Although high BP in PE can be managed with antihypertensive drugs, there is no effective treatment of FGR associated with PE. We have clarified that nicotinamide (Nam) alleviates PE-like condition and FGR induced by sFlt-1 in mice. But the mechanism of how Nam works is unclear. Objective Because Nam induces cytoprotective heme oxygenase 1 (HO-1), our aim was to clarify whether HO-1 contributes to therapeutic effect of Nam against FGR associated with PE. Methods We used chromium (III) mesoporphyrin (CrMP) to inhibit HO. We divided pregnant ICR wild type mice into 6 groups; control, Nam, sFlt-1, sFlt-1+Nam, sFlt-1+CrMP, sFlt-1+Nam+CrMP. sFlt-1 was overproduced by adenovirus administered at 14.5dpc. Nam and CrMP was given daily from 14.5dpc and 12.5dpc, respectively. Fetuses and placentae were harvested on 18.5dpc for analysis. Results Nam improved PE-like conditions and FGR induced by sFlt-1. CrMP 2μmol/kg/d exacerbated FGR and abolished its alleviation by Nam. CrMP 1.5μmol/kg/d did not affect FGR but Nam still alleviated FGR. Pregnancies in mice overproducing sFlt-1 continued longer with Nam, and CrMP abolished this effect of Nam. Conclusion HO plays a pivotal role in alleviation by Nam of FGR associated with PE.
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