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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

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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