Vasodilation effect of 2-benzyl-5-hydroxy-6-methoxy-3, 4-dihydroisoquinolin-1-one
Vasodilation effect of 2-benzyl-5-hydroxy-6-methoxy-3, 4-dihydroisoquinolin-1-one
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DOI：
10.1007/s12272-012-0818-z
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发表时间：
2012-08-01
影响因子：
6.7
通讯作者：
Cao, Yong-Xiao
中科院分区：
文献类型：
--
作者：
Xu, Wei-Qi;Xiong, Zhi-Zheng;Cao, Yong-Xiao
2-苄基-5-羟基-6-甲氧基-3, 4-二氢异喹啉-1-酮(ZC2)是一种新合成的异喹啉酮化合物。本研究评估了其对血管舒张的影响。通过体外灵敏的肌动描记系统记录大鼠动脉环的等长张力。结果表明，ZC2 以浓度依赖的方式松弛 KCl、去氧肾上腺素和 9, 11-双脱氧-11 α, 9 α-环氧甲烷-前列腺素 F2 α (U46619) 预收缩的大鼠肠系膜动脉，以及 KCl 预收缩的腹主动脉。 ZC2 诱导的血管舒张不受内皮剥脱的影响。 ZC2 以非平行方式向右移动 KCl、去氧肾上腺素和 5-羟色胺 (5-HT) 诱导的浓度-收缩曲线，这表明血管舒张作用很可能是通过电压依赖性钙通道 (VDCC) 和受体操作钙通道 (ROCC) 实现的。此外，在无 Ca2+ 培养基中，ZC2 浓度依赖性地抑制去氧肾上腺素和 CaCl2 诱导的血管收缩，并降低咖啡因诱导的收缩反应，这表明通过 VDCC 和 ROCC 抑制细胞外 Ca2+ 流入，以及通过兰尼碱受体从 Ca2+ 储存中释放细胞内 Ca2+。格列本脲不影响ZC2诱导的血管舒张，表明ATP敏感的钾通道不参与血管舒张。结果表明ZC2通过抑制VDCC和ROCC以及受体介导的Ca2+流入和释放来诱导血管舒张。细胞内 Ca2+ 释放的抑制可能是通过兰尼碱受体介导的。
A 2-Benzyl-5-hydroxy-6-methoxy-3, 4-dihydroisoquinolin-1-one (ZC2) is a newly synthesized isoquinolinone compound. Its effect on vasodilation was evaluated in the present study. Isometric tension of rat artery rings was recorded by a sensitive myography system in vitro. The results showed that ZC2 relaxed rat mesenteric arteries pre-contracted by KCl, phenylephrine and 9, 11- dideoxy- 11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha (U46619), and abdominal aorta pre-contracted by KCl in a concentration-dependent manner. The ZC2-induced vasodilation was not affected by an endothelium denudation. ZC2 rightwards shifted the concentration-contraction curves, induced by KCl, phenylephrine, and 5-hydroxytryptamine (5-HT) in a non-parallel manner, which suggests that the vasodilation effects are most likely via voltage-dependent calcium channel (VDCC) and receptor-operated calcium channel (ROCC). Moreover, in Ca2+-free medium, ZC2 concentration-dependently depressed the vasoconstrictions induced by phenylephrine and CaCl2, and decreased a contractile response induced by caffeine, which indicates a role of extracellular Ca2+ influx inhibition through VDCC and ROCC, and intracellular Ca2+ release from Ca2+ store via the ryanodine receptors. Glibenclamide did not affect the vasodilation induced by ZC2, suggesting that ATP sensitive potassium channel is not involved in the vasodilation. The results indicate that ZC2 induces vasodilation by inhibiting the VDCC and ROCC, and receptormediated Ca2+ influx and release. The inhibition of intracellular Ca2+ release may be mediated via the ryanodine receptors.