Mechanisms of the vasorelaxant effect of 1-hydroxy-2, 3, 5-trimethoxy-xanthone, isolated from a Tibetan herb, Halenia elliptica, on rat coronary artery.
Mechanisms of the vasorelaxant effect of 1-hydroxy-2, 3, 5-trimethoxy-xanthone, isolated from a Tibetan herb, Halenia elliptica, on rat coronary artery.
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DOI：
10.1016/j.lfs.2007.08.010
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发表时间：
2007-09
期刊：
影响因子：
6.1
通讯作者：
Yan Wang;Jiangong Shi;Mu-zou Wang;C. Che;J. Yeung
中科院分区：
文献类型：
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作者：
Yan Wang;Jiangong Shi;Mu-zou Wang;C. Che;J. Yeung
1-羟基-2，3，5-三甲氧基口山酮（HM-1）是从藏药椭圆花锚中分离得到的口山酮，HM-1（0.33-42.1 μM）对5-羟色胺（5-HT）预收缩的大鼠冠状动脉环有浓度依赖性舒张作用，EC_（50）为1.67±0.27 μM。内皮细胞的去除显著影响HM-1的血管扩张效力，导致Emax值降低46%。当加入一氧化氮合酶（NOS）抑制剂Nω-硝基-l-精氨酸甲酯（100 μM）或可溶性鸟苷酸环化酶抑制剂1H-[1，2，4]恶二唑并[4，3-α]喹喔啉-1-酮（ODQ，10 μM）后HM-1的血管舒张作用被抑制时，HM-1的内皮依赖性作用得到证实。阿托品（100 nM）、氟比洛芬（10 μM）、普萘洛尔（100 μM）、吡拉明（10 μM）、西咪替丁（10 μM）和SQ 22536（100 μM）对HM-1的血管舒张活性没有影响，表明不涉及其他受体/酶系统。在内皮剥脱的冠状动脉环中，HM-1的血管舒张作用不受钾通道阻滞剂如四乙基铵（10 mM）、伊比利亚毒素（100 nM）、氯化钡（100 μM）和4-氨基吡啶（1 mM）的影响。当HM-1（9.93 μM）部分消除CaCl 2诱导的血管收缩（在内皮完整的动脉环中抑制87%;在内皮剥脱的动脉环中抑制50%）时，证实了与无Ca 2+缓冲液孵育的5-HT致敏的动脉环制备物中Ca 2+通道的参与。在用无钙缓冲液孵育的KCl预处理制剂中，HM-1（9.93 μM）在内皮剥脱环中产生27.3%的抑制作用。HM-1（3.31-33.1 μM）对10 μM佛波醇12，13-二乙酸酯（PDA）在无钙溶液中产生的收缩反应具有最小的舒张作用（14.4%-20.3%），表明对细胞内Ca 2+机制的影响最小。这些研究结果表明HM-1的血管舒张作用涉及内皮依赖性机制（包括NO）和内皮非依赖性机制（通过抑制L型电压操纵性Ca 2+通道的Ca 2+内流）; HM-1的作用可能与抑制蛋白激酶C介导的细胞内Ca 2+储存释放有关。
1-Hydroxy-2, 3, 5-trimethoxyxanthone (HM-1) is a xanthone isolated from Halenia elliptica, a Tibetan medicinal herb. HM-1 (0.33–42.1 μM) produced a concentration-dependent relaxation in rat coronary artery rings pre-contracted with 1 μM 5-hydroxytryptamine (5-HT), with an EC50of 1.67±0.27 μM. Removal of the endothelium significantly affected the vasodilator potency of HM-1, resulting in 46% decrease in Emaxvalue. The endothelium-dependent effects of HM-1 was confirmed when its vasorelaxant effect was inhibited after addition of nitric oxide synthase (NOS) inhibitor Nω-nitro-l-arginine methyl ester (100 μM) or the soluble guanylate cyclase inhibitor 1H-[1, 2, 4] oxadiazolo [4,3-α] quinoxalin-1-one (ODQ, 10 μM). Atropine (100 nM), flurbiprofen (10 μM), propranolol (100 μM), pyrilamine (10 μM), cimetidine (10 μM) and SQ22536 (100 μM) had no effect on the vasorelaxant activity of HM-1 indicated the non-involvement of other receptor/enzyme systems. In endothelium-denuded coronary artery rings, the vasorelaxant effect of HM-1 was unaffected by potassium channel blockers such as tetraethylammonium (10 mM), iberiotoxin (100 nM), barium chloride (100 μM) and 4-aminopyridine (1 mM). The involvement of Ca2+channel in 5-HT-primed artery ring preparations incubated with Ca2+-free buffer was confirmed when HM-1 (9.93 μM) partially abolished the CaCl2-induced vasoconstriction (87% inhibition in intact-endothelium artery rings; 50% inhibition in endothelium-denuded rings). In the KCl-primed preparations incubated with Ca2+-free buffer, HM-1 (9.93 μM) produced a 27.3% inhibition in endothelium-denuded rings. HM-1 (3.31–33.1 μM) had minimal relaxant effects (14.4%–20.3%) on the contractile response generated by 10 μM phorbol 12,13-diacetate (PDA) in Ca2+-free solutions, suggesting minimal effects on intracellular Ca2+mechanisms. These findings suggest the vasodilator action of HM-1 involved both an endothelium-dependent mechanism involving NO and an endothelium-independent mechanism by inhibiting Ca2+influx through L-type voltage-operated Ca2+channels; a minor contribution to the effects of HM-1 may be related to inhibition of the protein kinase C-mediated release of intracellular Ca2+stores.