title: Functional and bioenergetic consequences of AT1 antagonist olmesartan medoxomil in hearts with postinfarction LV remodeling.
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.
authors.affiliation: Department of Medicine, University of Minnesota Health Sciences, Minneapolis, MN 55455, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ochiai
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Hu
authors.forename: Joseph
authors.initials: J
authors.lastname: Lee
authors.forename: Abdul
authors.initials: A
authors.lastname: Mansoor
authors.forename: Jingbo
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Guangrong
authors.initials: G
authors.lastname: Gong
authors.forename: Yo
authors.initials: Y
authors.lastname: Murakami
authors.forename: Yukada
authors.initials: Y
authors.lastname: Ishibashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Shimada
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels; D004734:Energy Metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000201:enzymology; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D000068557:Olmesartan Medoxomil; D010101:Oxygen Consumption; D010710:Phosphates / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000032:analysis; D012084:Renin-Angiotensin System / Q000187:drug effects; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D010710:Phosphates; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; D006180:Proton-Translocating ATPases