The vasorelaxant effect of evodiamine in rat isolated mesenteric arteries: mode of action

Abstract

The roles of the endothelium, Ca 2+ and K + fluxes in the evodiamine-induced attenuation of vascular contractile responses to vasoactive agents were examined. The results showed that: (1) in rat mesenteric artery rings, evodiamine elicited a concentration-dependent attenuation in the contractile response generated by phenylephrine. The inhibitory potency was greater for intact than for endothelium-denuded preparations. Thus, the vasodilator action of evodiamine appeared to be partially endothelium-interactive (dependent). (2) Evodiamine pretreatment had a greater inhibitory effect on the phenylephrine-induced tonic contraction (via Ca 2+ influx) than on the phasic contraction (via Ca 2+ release). In addition, evodiamine was more potent to inhibit the restoration by CaCl 2 of contractile responses to phenylephrine than a potassium depolarizing solution in media that had been kept calcium-free. These results suggest that block of the Ca 2+ influx through receptor-mediated Ca 2+ channels may be the major mechanism underlying the vasodilator effect of evodiamine. (3) A K + channel blocker, tetraethylammonium, almost completely abolished the vasodilatation induced by minoxidil (a known K + channel opener) but not evodiamine. The possible involvement of K + channel activation of the vasodilator effect produced by evodiamine was therefore excluded.