Beneficial effects of nicotinamide on the mouse model of preeclampsia.

Abstract

Preeclampsia (PE) is a pregnancy related disorder that is characterized by hypertension and proteinuria in the mother. It is associated with impaired coagulation and liver function, and a variety of other detrimental effects. In severe cases without treatment, PE can progress to eclampsia and result in seizures, a life-threatening condition. Although the etiology of PE is largely unknown, sFlt-1 (soluble vascular endothelial growth factor receptor 1) released by the impaired placenta resulting from insufficient perfusion plays a critical role in PE, and phenotypes of PE can be induced by experimentally increasing sFlt-1. We and other investigators have proposed that endothelin-1 (ET-1) system is the mediator of the pathological effects of excess sFlt-1, and antagonists of ET-1 receptor block the effects of sFlt-1. Unfortunately, this class of drugs is teratogenic and unsuitable for treating pregnant women. Nicotinamide is a naturally occurring derivative of vitamin B3 in the body and inhibits ADP-ribosyl cyclase, which is activated by the ET-1 receptor. Therefore, if utilized, it would be expected to play a beneficial role in PE. In mouse models of PE, a high dose of nicotinamide shows great success in lowering blood pressure, correcting renal function and structure, prolonging pregnancy as well as increasing fetal weight/number. Nicotinamide, being generally regarded as safe, could be a promising substance to further investigate for use in clinical trials.