Zhang Han, Liu Huanhuan, Chen Yulong, Zhang Yan
College of Pharmacy, Xi'an Medical University, Xi'an, Shaanxi, China.
Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi, China.
Ann Vasc Surg. 2018 Apr;48:233-240. doi: 10.1016/j.avsg.2017.09.007. Epub 2017 Sep 22.
Curcumin (Cur) is a natural lipophilic polyphenol compound extracted from the rhizome of turmeric. Recently, protective effect of Cur on cardiovascular system is paid close attention. Some researches demonstrated that Cur could induce vascular relaxation in many arterial beds. However, relaxant effect of Cur on rat superior mesenteric artery is not clear. This present study will investigate the vasorelaxant effect of Cur on rat superior mesenteric arteries and the mechanisms involved.
The isometric tension of rat superior mesenteric arterial rings was recorded by a sensitive myograph system in vitro. The vasodilation of Cur at various concentrations (range: 10-10 M) on potassium chloride (KCl; 60 mmol/L)-precontracted or phenylephrine hydrochloride (PE; 10 μmol/L)-precontracted arterial rings were observed. We also observed vasorelaxant effect of Cur on KCl (60 mM)-preconstricted rat superior mesenteric arterial rings after incubating the inhibitors of endothelial mechanism, including the endothelial nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester, the guanylate cyclase inhibitor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, and the cyclooxygenase inhibitor indomethacin, and inhibitors of potassium ion channel, including 4-aminopyridine (Voltage-sensitive K channel blockers), and tetraethylammonium chloride (Ca activated K channel blockers), and BaCl (Inward rectifying K channel blockers), and glibenclamide (ATP -sensitive K channel blockers), respectively. The effects of Cur are expressed as percentage of relaxation from the precontraction induced by KCl (60 mmol/L) or PE (10 μmol/L). The E value refers to the maximum relaxation. The pD value refers to the negative logarithmic value of the drug concentration that produces 50% E.
Cur concentration dependently relaxed the superior mesenteric artery rings with endothelium precontracted by PE (E = 84.33 ± 1.11 and pD = 5.03 ± 0.02) or KCl (E = 80.96 ± 2.12% and pD = 4.32 ± 0.01). The vasorelaxant effect of Cur on the superior mesenteric artery rings relied on endothelium partially. Indomethacin (5 μM) significantly inhibited the effect. However, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (10 μM) and Nω-nitro-L-arginine methyl ester (100 μM) had no effect on the action. In artery rings without endothelium, vasorelaxation induced by Cur was attenuated by 4-aminopyridine (100 μM). However, barium chloride dehydrate (10 μM), glibenclamide (10 μM), and traethylammonium chloride (1 mM) did not affect vasorelaxation induced by Cur. Moreover, Cur also significantly inhibited contraction induced by increasing external calcium in Ca-free medium plus K (60 mM) and releasing intracellular Ca in the Ca-free solution.
Our results suggested that Cur induces relaxation in superior mesenteric arterial rings through an endothelium-dependent pathway, involving prostanoid, and also through an endothelium-independent pathway, opening K channel, and blockade of Ca influx and intracellular Ca release.
姜黄素（Cur）是从姜黄根茎中提取的一种天然亲脂性多酚化合物。近年来，姜黄素对心血管系统的保护作用受到密切关注。一些研究表明，姜黄素可在许多动脉床诱导血管舒张。然而，姜黄素对大鼠肠系膜上动脉的舒张作用尚不清楚。本研究将探讨姜黄素对大鼠肠系膜上动脉的血管舒张作用及其相关机制。
采用灵敏的肌动描记系统体外记录大鼠肠系膜上动脉环的等长张力。观察不同浓度（范围：10 - 10 M）姜黄素对氯化钾（KCl；60 mmol/L）预收缩或盐酸去氧肾上腺素（PE；10 μmol/L）预收缩动脉环的舒张作用。我们还观察了姜黄素对KCl（60 mM）预收缩的大鼠肠系膜上动脉环在孵育内皮机制抑制剂（包括内皮型一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯、鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮和环氧合酶抑制剂吲哚美辛）以及钾离子通道抑制剂（包括4-氨基吡啶（电压敏感性钾通道阻滞剂）、氯化四乙铵（钙激活钾通道阻滞剂）、氯化钡（内向整流钾通道阻滞剂）和格列本脲（ATP敏感性钾通道阻滞剂））后的血管舒张作用。姜黄素的作用以相对于KCl（60 mmol/L）或PE（10 μmol/L）诱导的预收缩的舒张百分比表示。E值指最大舒张率。pD值指产生50% E的药物浓度的负对数值。
姜黄素浓度依赖性地舒张由PE预收缩（E = 84.33 ± 1.11，pD = 5.03 ± 0.02）或KCl预收缩（E = 80.96 ± 2.12%，pD = 4.32 ± 0.01）的带内皮的肠系膜上动脉环。姜黄素对肠系膜上动脉环的血管舒张作用部分依赖于内皮。吲哚美辛（5 μM）显著抑制该作用。然而，1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（10 μM）和Nω-硝基-L-精氨酸甲酯（100 μM）对该作用无影响。在无内皮的动脉环中，4-氨基吡啶（100 μM）减弱了姜黄素诱导的血管舒张。然而，二水合氯化钡（10 μM）、格列本脲（10 μM）和氯化四乙铵（1 mM）不影响姜黄素诱导的血管舒张。此外，姜黄素还显著抑制在无钙培养基加K（60 mM）中增加细胞外钙诱导的收缩以及在无钙溶液中释放细胞内钙诱导的收缩。
我们的结果表明，姜黄素通过涉及前列腺素的内皮依赖性途径以及通过开放钾通道、阻断钙内流和细胞内钙释放的内皮非依赖性途径诱导肠系膜上动脉环舒张。
