Functional and bioenergetic consequences of AT1 antagonist olmesartan medoxomil in hearts with postinfarction LV remodeling

Koichi Ochiai, Qingsong Hu, Joseph Lee, Abdul Mansoor, Jingbo Liu, Xiaohong Wang, Guangrong Gong, Yo Murakami, Yukada Ishibashi, Toshio Shimada, Jianyi Zhang

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The structural left ventricular (LV) remodeling and contractile dysfunction of hearts with postinfarction LV remodeling are benefited by angiotensin II type 1 receptor (AT1) blocker. However, the myocardial bioenergetic consequences of AT1 blocker in these hearts are not known. To investigate, we used a porcine model of postinfarction LV remodeling produced by ligation of the left circumflex coronary artery. After infarction, 7 pigs received olmesartan medoxomil (2 mg/kg) for comparison against 9 untreated and 10 normal pigs. Measurements of hemodynamics, myocardial perfusion, and myocardial bioenergetics were taken 7 weeks postinfarction. The treated group had an LV-to-body weight ratio significantly lower than the untreated group (2.69±0.70, 2.96±0.51, 3.66±0.60 g/kg for control, treated, and untreated groups, respectively). The untreated group had a mean aortic pressure significantly higher than the control (73±16, 86±14, and 94±20 mm Hg, respectively). The subendocardial phosphocreatine-to-ATP ratios of the treated group were significantly higher than that of the untreated group. The untreated group, but not the treated group, had significant reductions in mitochondrial F0F1-ATPase subunits compared with controls. Congestive heart failure as evidenced by significant ascites (100 to 2000 mL) developed in 4 of the 9 untreated animals, but was absent in the treated group. Animals with heart failure demonstrated reductions in both mitochondrial F0F1-ATPase expression and myocardial high-energy phosphate levels. Thus, severe LV dysfunction and accompanying abnormal myocardial bioenergetic phenotype were prevented by the AT1 antagonist olmesartan medoxomil.

Original languageEnglish (US)
Pages (from-to)686-694
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume47
Issue number5
DOIs
StatePublished - May 2006

Keywords

  • Heart failure
  • High-energy phosphates
  • Hypertrophy
  • Myocardial energetics
  • Myocardial infarction
  • Nuclear magnetic resonance spectroscopy

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