[PS 01-08] NICOTINAMIDE DECREASES BP IN MICE BY TWO MECHANISMS

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Abstract

Objective:

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.

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