Additive effects of combined blockade of AT1 receptor and HMG-CoA reductase on left ventricular remodeling in infarcted rats

Tsung-Ming Lee, Mei Shu Lin, Tsai Fwu Chou, Nen Chung Chang

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Abstract

Both angiotensin receptor antagonists and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to attenuate cardiomyocyte hypertrophy after myocardial infarction. Whether combination treatment may be superior to either drug alone on cardiomyocyte hypertrophy remains unclear. After ligation of the left anterior descending artery, rats were randomized to both, one, or neither of the angiotensin receptor antagonists olmesartan (0.01, 0.1, 1, and 2 mg·kg-1·day -1) and HMG-CoA reductase inhibitor pravastatin (5 mg·kg -1·day-1) for 4 wk. Each drug, when given alone, decreased cardiomyocyte sizes isolated by enzymatic dissociation at the border zone when compared with vehicles. However, compared with either drug alone, combined olmesartan and pravastatin prevent cardiomyocyte hypertrophy to a larger extent, which was further confirmed by downregulation of the left ventricular atrial natriuretic peptide mRNA. The myocardial endothelin-1 levels at the border zone were 6.5-fold higher (P

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number3
DOIs
Publication statusPublished - 2006

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Keywords

  • 3-hydroxy-3- methylgultaryl coenzyme A
  • Arrhythmias
  • Hypertrophy
  • Myocardial infarction
  • Myocytes

ASJC Scopus subject areas

  • Physiology

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