Ligustilide induces vasodilatation via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release

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 μM 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 (CaCl2), 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 β-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 CaCl2 in Ca2+-free medium, indicating that the vasodilatation relates to inhibition of extracellular Ca2+ influx through VDCC and ROCC, and intracellular Ca2+ release from Ca2+ store. Since caffeine-induced contraction was inhibited by ligustilide, inhibition of intracellular Ca2+ 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 Ca2+ influx and release.