The vasorelaxant effect of evodiamine in rat isolated mesenteric arteries: mode of action.
The roles of the endothelium, Ca2+ 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 Ca2+ influx) than on the phasic contraction (via Ca2+ release). In addition, evodiamine was more potent to inhibit the restoration by CaCl2 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 Ca2+ influx through receptor-mediated Ca2+ 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.
Chiou
W F
WF
National Research Institute of Chinese Medicine, Taipei Hsien, Taiwan.
Chou
C J
CJ
Shum
A Y
AY
Chen
C F
CF
D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects; D002122:Calcium Chloride / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D015220:Calcium Channels; D010936:Plant Extracts; D015221:Potassium Channels; D011799:Quinazolines; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D010656:Phenylephrine; C049639:evodiamine; D002122:Calcium Chloride; D002118:Calcium