title: Ligustilide induces vasodilatation via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release.
abstract: The purpose of the present study was to investigate the effect of ligustilide on vasodilatation in rat mesenteric artery and the mechanisms responsible for it. Isometric tension of rat mesenteric artery rings was recorded by a sensitive myograph system in vitro. The results showed that ligustilide at concentrations more than 10 microM relaxed potassium chloride (KCl)-preconstricted rat mesenteric artery in a concentration-dependent manner. The vasodilatation effect of ligustilide was not dependent on endothelium. Ligustilide rightwards shifted concentration-response curves induced by KCl, calcium chloride (CaCl(2)), noradrenaline (NA) or 5-hydroxytryptamine (5-HT) in a non-parallel manner. This suggests that the vasodilatation effects were most likely via voltage-dependent calcium channel (VDCC) and receptor-operated calcium channel (ROCC). Propranolol, glibenclamide, tetraethylammonium and barium chloride did not affect the vasodilation induced by ligustilide, showing that beta-adrenoceptor, ATP sensitive potassium channel, calcium-activated potassium channel and inwardly rectifying potassium channel were not involved in the vasodilatation. Ligustilide concentration-dependently inhibited the vasoconstriction induced by NA or CaCl(2) in Ca(2+)-free medium, indicating that the vasodilatation relates to inhibition of extracellular Ca(2+) influx through VDCC and ROCC, and intracellular Ca(2+) release from Ca(2+) store. Since caffeine-induced contraction was inhibited by ligustilide, inhibition of intracellular Ca(2+) released by ligustilide occurred via the ryanodine receptors. Our results suggest that ligustilide induces vasodilatation in rat mesenteric artery by inhibiting the VDCC and ROCC, and receptor-mediated Ca(2+) influx and release.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, and Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, PR China. yxy@xjtu.edu.cn
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jian-Yu
authors.initials: JY
authors.lastname: He
authors.forename: Lang-Chong
authors.initials: LC
authors.lastname: He
authors.forename: Cang-Bao
authors.initials: CB
authors.lastname: Xu
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D009213:Myography; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D012701:Serotonin; D002110:Caffeine; C027820:ligustilide; D011189:Potassium Chloride; D002122:Calcium Chloride; D015107:4-Butyrolactone; D002118:Calcium; D009638:Norepinephrine