Abstract

This article examines the mechanism of action of 12-hydroxynorfluorocurarine hydrochloride on vascular contractile activity. The studies were conducted in vitro using rat aortic rings. The isometric force of the contractile force of the rings was measured using an FT-03 force transducer (Grass Instrument, USA). 12-Hydroxynorfluorocurarine hydrochloride produced a dose-dependent vasorelaxant response on phenylephrine-induced aortic ring contractility, with the vasorelaxant response being reduced in the absence of endothelium. The vasorelaxant effect of 12-hydroxynorfluorocurarine hydrochloride is driven by modulation of the endothelial NO synthase (eNOS), guanylate cyclase (sGC), inward-rectifier K+ channels (Kir), and Ca2+-activated K+ channels. Furthermore, when 50 mM KCl is present, this indole alkaloid was observed to diminish the force of aortic contraction induced by elevated Ca²? ion concentration. 12-Hydroxynorfluorocurarine hydrochloride has been shown to exert potent vasorelaxant effects on rat aortic preparations through both endothelium-dependent and endothelium-independent pathways. It has been shown that the vasorelaxant action of 12- hydroxynorfluorocurarine hydrochloride is mediated by blocking L-type Ca2+ channels via the eNOS/NO/sGC signalling cascade and by activating Kir channels.

Key words: indole alkaloid, aorta, vasorelaxant, endothelium, ion channel.