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氯沙坦对大鼠肥厚心肌L-型钙电流的作用

傅丽英, 李泱, 程岚, 王芳, 夏国瑾, 姚伟星   

  1. 华中科技大学同济医学院药理教研室, 武汉 430030
  • 收稿日期:2001-02-22 修回日期:2001-04-13 出版日期:2001-06-15 发布日期:2001-06-15

Effects of Losartan on L-type Calcium Current in Hypertrophied Rat Myocytes

Fu Liying, Li Yang, Cheng Lan, Wang Fang, Xia Guojin, Yao Weixing   

  1. Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030
  • Received:2001-02-22 Revised:2001-04-13 Online:2001-06-15 Published:2001-06-15

摘要: 目的: 研究腹主动脉结扎诱发大鼠肥厚心肌L-型钙电流的变化以及用氯沙坦治疗对此变化的影响。方法: 用结扎腹主动脉的方法诱发大鼠心肌肥厚模型。用全细胞膜片钳技术记录肥厚左心室肌细胞L-型钙电流。结果: 肥厚组心肌细胞膜电容(148±29 pF) 明显大于假手术组(102±14 pF, P<0.01) 和氯沙坦治疗组(118±27, P<0.01)。肥厚组ICa,L峰值及电流密度均大于假手术组(-835±124 pA vs -1404±417 pA (7.5±1.8 pA·pF-1 vs -0.5±2.2 pA·pF-1, P<0.01)。氯沙坦治疗组ICa,L 峰值(-956±170 pF) 及电流密度(-8.2±1.6 pA·pF-1) 均比肥厚组明显减小(P<0.05)。肥厚组半数激活电压(-20.6±1.0 mV)与假手术组(-15.6±1.6 mV) 及氯沙坦治疗组(-17.4±1.0 mV) 相比向负向移动(P<0.01)。肥厚组激活曲线斜率(5.7±0.4)比假手术组(6.4±0.5) 略减小(P<0.05)。肥厚组半数失活电压(-27.6±1.9 mV) 比假手术组(-31.4±2.2 mV) 略正移(P<0.05)。三组心肌失活曲线斜率无差异。结论: 氯沙坦(30 mg·kg-1·d-1, ig) 可防止腹主动脉结扎诱发大鼠心肌细胞肥大的发生及相关的L-型钙电流的变化。

关键词: 氯沙坦, 心肌肥厚, 膜片钳, 钙电流

Abstract: Objective To investigate the alterations of L-type calcium current (ICa,L) in abdominal aortic ligation-induced hypertrophied rat hearts and the effect of losartan on these alterations. Methods Cardiac hypertrophy was induced by abdominal aortic ligation in rats. To record ICa,L, whole-cell patch-clamp technique was used. Results Membrane capacitance was larger in hypertrophied cells (148±29 pF) than in sham-operated cells (102±14 pF, P<0.01) and losartan-treated cells (118±27, P<0.01). The maximal peak ICa,L was increased from -835±124 pA in sham-operated cells to -1404±417 pA in hypertrophied cells (P<0.01), the corresponding ICa,L density was increased from -7.5±1.8 pA·pF-1 to -10.5±2.2 pA·pF-1 (P<0.01), while they were reduced to -956±170 pF (P<0.01) and -8.2±1.6 pA·pF-1 (P<0.05) respectively in losartan-treated cells. The membrane potential of half maximal activation of the hypertrophied cells (-20.6±1.0 mV) shifted to more negative potentials than sham-operated cells (-15.6±1.6 mV, P<0.01) and lorsartan-treated cells (-17.4±1.0 mV, P<0.01). The slope of the activation curve of hypertrophied cells (5.7±0.4) was decreased slightly than sham-operated cells (6.4±0.5, P<0.05). The membrane potential of half maximal inactivation of hypertrophied cells (-27.6±1.9 mV) shifted to more positive potentials than sham-operated cells (-31.4±2.2 mV, P<0.05). The slope of inactivation curves were not different in the three groups. Conclusion Treatment with losartan (30 mg·kg-1·d-1, ig) prevented the cell enlargement and the alterations of ICa,L in abdominal aortic ligation-induced hypertrophied rat hearts.

Key words: Losartan, Cardiac hypertrophy, Patch-clamp technique, L-type calcium current

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