Nicotinamide (Nam) is an inhibitor of ADP ribosyl cyclase (ADPRC), and is an effective vasodilator of vessels already constricted by ET-1. ET-1 acts on ETAR, and constricting vascular smooth muscle by releasing Ca2+ from intracellular stores. Nam ameliorates the high BP in mice induced by excess sFlt-1. The aim of this study is to clarify the mechanism of action of Nam.Design and Method:
We measured tail-cuff BP before and after administering sFlt-1 in WT and mice lacking CD38 (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 prevented sFlt-1 induced hypertension and diminished 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:
Nicotinamide 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.