Paeonol induces vasodilatation in rat mesenteric artery via inhibiting extracellular Ca2+ influx and intracellular Ca2+ release

To investigate the vasodilative effect of paeonol in rat mesenteric artery and the mechanisms responsible for it. Rats were anaesthetized and sacrificed. The superior mesenteric artery was removed, dissected free of adherent tissue and cut into 2.0 mm long cylindrical segments. Isometric tension of artery rings was recorded by a myograph system in vitro. Concentration-relaxation curves of paeonol (17.8 mu mol/L to 3.16 mmol/L) were recorded on artery rings precontracted by potassium chloride (KCl) and concentration-contraction curves of KCl, 5-hydroxytryptamine (5-HT), noradrenaline (NA) or calcium chloride (CaCl2) were recorded in the presence of paeonol (10(-4.5), 10(-3.8), 10(-3.5) mol/L) respectively. And also, concentrationrelaxation curves of paeonol were recorded in the presence of different potassium channel inhibitors and propranolol on rings precontracted with KCl respectively. To investigate the role of intracellular Ca2+ release from Ca2+ store, the contraction induced by NA (100 mu mol/L) and CaCl2 (2 mmol/L) in Ca2+ free medium was observed in the presence of paeonol respectively. Paeonol relaxed artery rings precontracted by KCl in a concentration-dependent manner and the vasodilatation effect was not affected by endothelium denudation. Paeonol significant decreased the maximum contractions (E-max) induced by KCl, CaCl2, NA and 5-HT, as well as E-max induced by NA and CaCl2 in Ca2+ -free medium, suggesting that paeonol dilated the artery via inhibiting the extracellular Ca2+ influx mediated by voltage-dependent calcium channel, and receptor-mediated Ca2+-influx and release. Moreover, none of glibenclamide, tetraethylammonium, barium chlorded and propranolol affected the paeonol-induced vasodilatation, indicating that the vasodilatation was not contributed to ATP sensitive potassium channel, calcium-activated potassium channel, inwardly rectifying potassium channel, and beta-adrenoceptor. Paeonol induces non-endothelium dependent-vasodilatation in rat mesenteric artery via inhibiting voltage-dependent calcium channel-mediated extracellular Ca2+ influx and receptor-mediated Ca2+ influx and release.