title: Exercise training restores aerobic capacity and energy transfer systems in heart failure treated with losartan.
abstract: OBJECTIVE
  Clinical and experimental studies demonstrate that exercise training improves aerobic capacity and cardiac function in heart failure, even in patients on optimal treatment with angiotensin inhibitors and beta-blockers, but the cellular mechanisms are incompletely understood. Since myocardial dysfunction is frequently associated with impaired energy status, the aim of this study was to assess the effects of exercise training and losartan on myocardial systems for energy production and transfer in heart failure.
  
  
  METHODS
  Maximal oxygen uptake, cardiac function and energy metabolism were assessed in heart failure after a myocardial infarction induced by coronary artery ligation in female Sprague-Dawley rats. Losartan was initiated one week after infarction and exercise training after four weeks, either as single interventions or combined. Animals were sacrificed 12 weeks after surgery.
  
  
  RESULTS
  Heart failure, confirmed by left ventricular diastolic pressure >15 mmHg and by >20 mmHg drop in peak systolic pressure, was associated with 40% lower aerobic capacity and significant reductions in enzymes involved in energy metabolism. Combined treatment yielded best improvement of aerobic capacity and ventricular pressure characteristics. Exercise training completely restored aerobic capacity and partly or fully restored creatine and adenylate kinases, whereas losartan alone further reduced these enzymes. In contrast, losartan reduced left ventricle diastolic pressure, whereas exercise training had a neutral effect.
  
  
  CONCLUSIONS
  Exercise training markedly improves aerobic capacity and cardiac function after myocardial infarction, either alone or in combination with angiotensin inhibition. The two interventions appear to act by complementary mechanisms; whereas exercise training restores cardiac energy metabolism, mainly at the level of energy transfer, losartan unloads the heart by lowering filling pressure and afterload.
authors.affiliation: Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Ole Johan
authors.initials: OJ
authors.lastname: Kemi
authors.forename: Morten Andre
authors.initials: MA
authors.lastname: Høydal
authors.forename: Per Magnus
authors.initials: PM
authors.lastname: Haram
authors.forename: Anne
authors.initials: A
authors.lastname: Garnier
authors.forename: Dominique
authors.initials: D
authors.lastname: Fortin
authors.forename: Renee
authors.initials: R
authors.lastname: Ventura-Clapier
authors.forename: Oyvind
authors.initials: O
authors.lastname: Ellingsen
mesh_terms: D000263:Adenylate Kinase / Q000032:analysis; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003131:Combined Modality Therapy; D003402:Creatine Kinase / Q000032:analysis; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000032:analysis; D004735:Energy Transfer; D005081:Exercise Therapy; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000628:therapy*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D019808:Losartan / Q000627:therapeutic use*; D008565:Membrane Proteins / Q000235:genetics; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D008565:Membrane Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D007770:L-Lactate Dehydrogenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D003402:Creatine Kinase; D000263:Adenylate Kinase; D019808:Losartan