川阿格雷钠舒张血管的作用及机制研究

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (9): 1001-1006.

川阿格雷钠舒张血管的作用及机制研究

包许, 李晨辉, 徐珺, 吴玉林

中国药科大学生理教研室,南京 211198,江苏

收稿日期:2012-04-11 修回日期:2012-06-18 发布日期:2012-09-25
通讯作者: 吴玉林,通信作者,男,博士,副教授,研究方向:心血管药理学。Tel: 13809002136 E-mail: wylcpu@yahoo.com.cn
作者简介:包许,女,硕士在读,研究方向:心血管药理学。Tel: 13913040860 E-mail: tonghua2166@163.com

Vasodilation effect of MC-002 and its possible mechanisms

BAO Xu, LI Chen-hui, XU Jun, WU Yu-lin

Department of Physiology, China Pharmaceutical University, Nanjing 211198, Jiangsu, China

Received:2012-04-11 Revised:2012-06-18 Published:2012-09-25

摘要/Abstract

摘要： 目的研究川阿格雷钠(MC-002)对大鼠胸主动脉的舒张作用,并探讨其可能的作用机制。方法测定川阿格雷钠对去甲肾上腺素(NE)和高钾预收缩的大鼠胸主动脉血管环的舒张作用,并观察L-硝基精氨酸甲酯(L-NAME)、亚甲蓝、吲哚美辛、格列本脲、蜂毒明肽、氯化钡和4-氨基吡啶对其作用的影响。结果川阿格雷钠(3~300 μmol/L)能浓度依赖性地舒张NE预收缩的完整血管环,去内皮、亚甲蓝孵育和吲哚美辛孵育均能显著抑制其舒血管作用(P<0.05,P<0.01),L-NAME孵育无显著影响。川阿格雷钠拮抗高钾诱导完整血管环收缩的作用被格列本脲(ATP敏感型钾通道KATP抑制剂)和蜂毒明肽(小传导性钙激活型钾通道SKCa抑制剂)显著降低(P<0.01),氯化钡和4-氨基吡啶无显著影响。川阿格雷钠使NE预收缩的血管平滑肌的钙浓度-收缩曲线下移、右移,且呈现浓度依赖性。结论川阿格雷钠可能通过内皮细胞的鸟苷酸环化酶途径和环氧合酶途径、开放KATP和SKCa引起平滑肌细胞膜超极化以及减少钙内流而松弛血管。

关键词: 川阿格雷钠, L-硝基精氨酸甲酯, 亚甲蓝, 吲哚美辛, 钾通道抑制剂

Abstract: AIM: To investigate the vasodilation effect of MC-002 and its possible mechanisms. METHODS: The relaxation effect of MC-002 on rat aortic rings which was pre-constricted by norepinephrine or high-potassium Krebs’solution was measured and the influences of pretreatment with NG-Nitroarginine Methyl Ester (L-NAME), methylene blue, indometacin, glibenclamide ,apamin, barium chloride and 4-aminopyridine on this vasorelaxation effect were observed.RESULTS: MC-002(3-300μmol/L) showed a concentration-dependent dilation effect on rat aortic rings pre-constricted by norepinephrine. Endothelium denudation, pretreatment with methylene blue and indometacin incubation significantly blunted this effect whereas L-NAME did not affect it.Pre-incubation of glibenclamide or apamin, rather than Barium chloride or 4-aminopyridine, apparently inhibited vasodilation effect of MC-002 antagonizing high-potassium Krebs’ solution.The CaCl₂-induced contraction curves of endothelium-denuded arteries stimulated with norepinephrine(300 nmol/L ) in calcium-free medium were significantly shifted to the right and downward, in comparison with controls after pre-incubation with MC-002(10^-5 and 10^-4 mol/L) in a concentration-dependent manner.CONCLUSION: MC-002 had a vasorelaxation effect mediated by guanylate cyclase and cyclooxygenase pathway which was endothelium-dependent, and opening of KATP and SKCa channels which caused hyperpolarization along with the inhibition of calcium influx in smooth muscle cells could contribute to endothelium-independent relaxation.

Key words: MC-002, L-NAME, Methylene blue, Indometacin, Inhibiter of potassium channels

中图分类号:

R965.2

包许, 李晨辉, 徐珺, 吴玉林. 川阿格雷钠舒张血管的作用及机制研究[J]. 中国临床药理学与治疗学, 2012, 17(9): 1001-1006.

BAO Xu, LI Chen-hui, XU Jun, WU Yu-lin. Vasodilation effect of MC-002 and its possible mechanisms[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(9): 1001-1006.

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