Mechanism of vasorelaxation of thoracic aorta caused by xanthone

The effect of xanthone on smooth muscle was studied in thoracic aorta isolated from rats. Xanthone relaxed the norepinephrine-induced contraction of rat thoracic aorta. This relaxing effect of xanthone persisted in endothelium-denuded aorta suggesting that the relaxation induced by xanthone is endothelium-independent. The norepinephrine and high-K⁺-induced vasoconstriction was inhibited dose dependently in aorta pretreated with xanthone with IC₅₀ values of 60.26 ± 8.43 and 82.9 ± 13.21 μM, respectively. The inositol 1,4,5-trisphosphate formation induced by norepinephrine (3 μM) in rat aorta was not affected by xanthone (10-100 μM), suggesting that the vasorelaxant effect of xanthone was not exerted on the receptor. Xanthone concentration dependently inhibited the ⁴⁵Ca²⁺ influx induced by either norepinephrine or high-K⁺, suggesting that xanthone might act as a blocker of both receptor-operated and voltage-dependent Ca²⁺ channels. Furthermore, xanthone caused an increase in the level of intracellular cyclic adenosine 3',5'-monophosphate (cAMP), but not cyclic guanosine 3',5'-monophosphate (cGMP) content. These data suggested that the mechanism of xanthone-induced vasorelaxation might involve the increase of intracellular cyclic adenosine 3',5'-monophosphate (cAMP) content and block of Ca²⁺ channels.