OS 21-05 PIVOTAL ROLE OF HEME OXYGENASE IN AMELIORATION BY NICOTINAMIDE OF FETAL GROWTH RESTRICTION ASSOCIATED WITH PREECLAMPSIA.

OBJECTIVE: Preeclampsia (PE) is pregnancy-induced hypertension with proteinuria. It causes maternal death or fetal growth restriction (FGR). Although high BP 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 soluble fms-like tyrosine kinase-1 (sFlt-1) in mice. But the mechanism of how Nam works is unclear. Because Nam induces cytoprotective heme oxygenase 1 (HO-1), our aim is to clarify whether HO-1 contributes to therapeutic effect of Nam against FGR associated with PE.

DESIGN AND METHOD: 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 14.5 dpc. Nam and CrMP was given daily from 14.5 dpc and 12.5 dpc respectively. Fetuses and placentae were harvested on 18.5 dpc for analysis.

RESULTS: Nam improved PE-like conditions and FGR induced by sFlt-1. CrMP 2 μmol/kg/d exacerbated FGR and abolished its alleviation by Nam. CrMP 1.5 μmol/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.

CONCLUSIONS: HO plays a pivotal role in alleviation by Nam of FGR associated with PE.