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中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (2): 155-159.

• 基础研究 • 上一篇    下一篇

H2S对大鼠大脑中动脉平滑肌细胞膜电位的超极化作用

蔡圣年, 范一菲, 陈志武   

  1. 安徽医科大学药理学教研室,合肥 230032,安徽
  • 收稿日期:2011-01-07 修回日期:2011-02-18 发布日期:2011-04-20
  • 通讯作者: 陈志武,男,教授,博士生导师,研究方向:心脑血管药理学。Tel: 0551-5161133 E-mail: wzcxiong@mail.hf.ah.cn
  • 作者简介:蔡圣年,女,硕士研究生,研究方向:心脑血管药理学。Tel: 18956046932 E-mail: caishengnian@163.com
  • 基金资助:
    高等学校博士学科点专项科研基金(2005Z031);国家自然科学基金(30840104)

Hyperpolarization of hydrogen sulfide on the membrane potential of vascular smooth muscle cell in rat middle cerebral artery

CAI Sheng-nian, FAN Yi-fei, CHEN Zhi-wu   

  1. Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui ,China
  • Received:2011-01-07 Revised:2011-02-18 Published:2011-04-20

摘要: 目的:探讨大鼠大脑中动脉(middle cerebral artery,MCA)内皮源性超极化因子(endothelium-derived hyperpolarizing factor,EDHF)介导的平滑肌细胞(VSMC) 静息膜电位超极化作用与硫化氢(hydrogen sulfide,H2S)的关系。方法: 采用大鼠离体MCA的VSMC静息膜电位记录实验,观察乙酰胆碱(ACh)、硫氢化钠(NaHS,H2S外源性供体)等的超极化作用。结果: ACh可使大鼠MCA的VSMC发生浓度依赖性超极化,用NO合酶抑制剂(L-NAME,3×10-5 mol /L)和前列环素(PGI2)合成酶抑制剂(Indo,10-5 mol/L)预处理后,ACh对大鼠MCA的VSMC仍有明显的超极化,即非NO、非PG2介导的超极化。钙激活钾通道的阻断剂四乙胺(TEA,1×10-3 mol/L)或H2S合成酶 (胱硫醚-γ-裂解酶,CSE)的抑制剂DL-炔丙基甘氨酸(PPG,10-4 mol/L)均可明显取消这种非NO、非PG2介导的超极化。H2S供体NaHS [(10-5 ~10-2.5) mol/L]对大鼠MCA的VSMC产生浓度依赖性的超极化作用,而1×10-3 mol/L TEA可以抑制其超极化作用。结论:大鼠MCA非NO、非PGI2介导的VSMC超极化作用,即EDHF反应可能是H2S介导的。

关键词: 内皮源性超极化因子, 硫化氢, 大鼠大脑中动脉, 平滑肌细胞, 静息膜电位, 超极化

Abstract: AIM: To study the hyperpolarizing effect of hydrogen sulfide (H2S) and endothelium-derived hyperpolarizing factor (EDHF) on the resting membrane potential of vascular smooth muscle cell (VSMC) in rat middle cerebral artery (MCA).METHODS: By using the record of resting membrane potential of VSMC in the isolated rat MCAs, the hyperpolarizing effects of acetylcholine (ACh), NaHS were detected, respectively.RESULTS:In rat MCAs, 10-7-10-4.5 mol/L ACh had significant and concentration-dependent hyperpolarizing effect on the resting membrane potential of VSMC in the absence and presence of 3×10-5 mol/L Nω-nitro-L-arginine-methyl-ester (L-NAME, an inhibitor of nitric oxide synthase) and 1×10-5 mol/L indomethacin (Indo, an inhibitor of PGI2 synthesis). The hyperpolarizing effect of ACh in the presence of L-NAME and Indo was almost abolished by tetraethylammonium (TEA, an inhibitor of calcium-activated K+ channels at 1×10-3 mol/L) or 1×10-4 mol/L DL-propargylglycine (PPG), an inhibitor of endogenous H2S synthase (cystathionine-γ-lyase, CSE). NaHS, a donor of H2S had the concentration-dependent hyperpolarizing effect on the resting membrane potential of VSMC in rat MCAs, and the hyperpolarization was markedly inhibited by 1×10-3 mol/L TEA.CONCLUSION: H2S might mediate the non-NO- non-PGI2 hyperpolarization, the so-called EDHF response on the resting membrane potential of VSMC in rat MCAs.

Key words: Endothelium-dependent hyperpolarizing factor, Hydrogen sulfide, Rat middle cerebral artery, Vascular smooth muscle cell, Resting membrane potential, Hyperpolarization

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