Differential Impact of Atorvastatin vs Pravastatin on Progressive Insulin Resistance and Left Ventricular Diastolic Dysfunction in a Rat Model of Type II Diabetes

• Chen Yan

  Department of Cardiorenal Cerebrovascular Medicine, Kagawa University School of Medicine

• Ohmori Koji

  Department of Cardiorenal Cerebrovascular Medicine, Kagawa University School of Medicine

• Mizukawa Mizuki

  Department of Cardiorenal Cerebrovascular Medicine, Kagawa University School of Medicine

• Yoshida Junji

  Department of Cardiorenal Cerebrovascular Medicine, Kagawa University School of Medicine

• Zeng Yu

  Department of Urology, Kagawa University School of Medicine

• Zhang Ling

  Department of Cardiovascular Physiology, Kagawa University School of Medicine

• Shinomiya Kaori

  Department of Cardiorenal Cerebrovascular Medicine, Kagawa University School of Medicine

• Kosaka Hiroaki

  Department of Cardiovascular Physiology, Kagawa University School of Medicine

• Kohno Masakazu

  Department of Cardiorenal Cerebrovascular Medicine, Kagawa University School of Medicine

抄録

Background Controversy exists regarding the effects of statin therapy on progressive insulin resistance (IR) and its consequences, in the present study a rat model of spontaneously developing type II diabetes mellitus (DM) was used to examine the impact of atorvastatin (AS) vs pravastatin (PS). Methods and Results The Otsuka Long-Evans Tokushima Fatty rats were either untreated or treated with 100 mg/kg per day of AS or PS from 6 weeks of age for 24 weeks. AS achieved much greater lipid lowering than PS. Serial oral glucose tolerance tests revealed new-onset diabetes was delayed by PS only. The untreated rats exhibited a progressive decrease in plasma adiponectin, increases in plasma leptin and tumor necrosis factor-α, and reduction of plasma nitric oxide (NO), which were limited more by PS than AS. PS, but not AS, enhanced adiponectin mRNA expression in white adipose tissue at 30 weeks. Cardiac endothelial NO synthase expression was upregulated, and overexpression of both transforming growth factor-β1 and monocyte chemoattractant protein-1 mRNA was limited more by PS than AS. Coronary perivascular fibrosis at 30 weeks was suppressed only by PS, which was accompanied by preserved left ventricular diastolic function assessed with Doppler echocardiography. Conclusions The moderate lipid lowering by PS, but not the intensive lipid lowering by AS, prevented new-onset DM and diastolic dysfunction in a rat model of IR, and this was associated with preferable adipocytokine profiles and cardiac redox states. (Circ J 2007; 71: 144 - 152)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 71 (1), 144-152, 2007

  一般社団法人 日本循環器学会

キーワード

• Adiponectin
• Diastolic dysfunction
• Doppler echocardiography
• Lipid-lowering therapy
• Nitric oxide

詳細情報

• CRID: 1390282680079682176
• NII論文ID: 110006151879
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.71.144
• ISSN: 13474820
• ISSN: 13469843
• ISSN: http://id.crossref.org/issn/13469843
• Web Site: http://www.jstage.jst.go.jp/article/circj/71/1/71_1_144/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2007190436
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可