31 Depressor mechanisms of nicotinamide in preeclampsia

Abstract

Introduction Nicotinamide (Nam) inhibits ADP ribosyl cyclase (ADPRC), diminishes a release of Ca2+ from intracellular stores, and dilates vessels constricted by endothelin-1 (ET-1). We previously reported that Nam ameliorates the high BP in mice induced by excess sFlt-1. Objective The aim of this study is to clarify the mechanism of action of Nam. Methods We measured tail-cuff BP before and after administering sFlt-1 in WT and mice lacking CD38 (which codes for the major form of ADPRC). We next measured SBP by telemetry to investigate short-term effects of Nam, DAB (2,2′-dihydroxyazobenzene, a specific inhibitor of ADPRC) and CrMP (chromium mesoporphyrin, a specific inhibitor of heme oxygenase). Results Lack of CD38 prevents sFlt-1 induced hypertension and diminishes the decrease in SBP by Nam. DAB decreased SBP in a magnitude similar to that by Nam, but the hypotensive effect of DAB lasted shorter than that of Nam. Pretreatment of CrMP made the hypotensive effect of Nam shorter than Nam. Conclusions Nam decreases BP in mice by two mechanisms: one which is shorter acting and probably depends on the ability of Nam to inhibit ADPRC, and a second longer acting mechanism which depends on the ability of Nam to increase the production of HO-1. Nicotinamide is a promising treatment of hypertension in PE.