The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Metformin Inhibits Isoproterenol-induced Cardiac Hypertrophy in Mice

  • Cha, Hye-Na (Department of Physiology, College of Medicine, Yeungnam University) ;
  • Choi, Jung-Hyun (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Kim, Yong-Woon (Department of Physiology, College of Medicine, Yeungnam University) ;
  • Kim, Jong-Yeon (Department of Physiology, College of Medicine, Yeungnam University) ;
  • Ahn, Myun-Whan (Department of Orthopedics, College of Medicine, Yeungnam University) ;
  • Park, So-Young (Department of Physiology, College of Medicine, Yeungnam University)
  • Received : 2010.10.02
  • Accepted : 2010.12.07
  • Published : 2010.12.31
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Abstract

The present study examined whether metformin treatment prevents isoporterenol-induced cardiac hypertrophy in mice. Chronic subcutaneous infusion of isoproterenol (15 mg/kg/24 h) for 1 week using an osmotic minipump induced cardiac hypertrophy measured by the heart-to-body weight ratio and left ventricular posterior wall thickness. Cardiac hypertrophy was accompanied with increased interleukin-6 (IL-6), transforming growth factor (TGF)-${\beta}$, atrial natriuretic peptide (ANP), collagen I and III, and matrix metallopeptidase 2 (MMP-2). Coinfusion of metformin (150 mg/kg/24 h) with isoproterenol partially inhibited cardiac hypertrophy that was followed by reduced IL-6, TGF-${\beta}$, ANP, collagen I and III, and MMP-2. Chronic subcutaneous infusion of metformin did not increase AMP-activated protein kinase (AMPK) activity in heart, although acute intraperitoneal injection of metformin (10 mg/kg) increased AMPK activity. Isoproterenol increased nitrotyrosine levels and mRNA expression of antioxidant enzyme glutathione peroxidase and metformin treatment normalized these changes. These results suggest that metformin inhibits cardiac hypertrophy through attenuating oxidative stress.

Keywords

References

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