Exercise training restores aerobic capacity and energy transfer systems in heart failure treated with losartan

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. Conclusion: 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

Exercise training does/does not induce vascular adaptations beyond the active muscle beds

The question whether exercise induces adaptations in nonactive muscle arteries (1, 5) cannot be answered by a simple yes or no. We believe that the effect in nonactive muscle beds is best viewed as a balance with the individual's exercise tolerance, lipid and glucose status, and blood pressure on the one side, and exercise intensity and degree of improvement of lipid, glucose, and blood pressure status on the other side. A low-intensity exercise program in healthy subjects, by abovementioned measures, may therefore induce little or no improvement in endothelial function, whereas a high-intensity program might (3). In contrast, in situations of reduced cardiovascular and metabolic health, such as heart failure, hypertension, diabetes, and hypercholesterolemia, exercise may readily improve endothelial function in all vascular beds. This has been suggested by both brachial artery plethysmography and imaging, and organ bath experiments of the left internal mammary artery (2, 6). Further support for exercise-induced adaptation in nonactive arteries stems from studies of treadmill-exercised rodents, which improve carotid artery endothelium-dependent nitric oxide (NO)-mediated vasorelaxation (4). Supposedly, the carotid artery does not supply exercising muscles. Intracellularly, improved endothelial function has been linked to higher activities of endothelial NO synthase and Akt (2), suggesting the cell may sense shear stress even in nonactive regions. Thus clinical and experimental evidence suggest that the artery is in a state of continuum, in which the susceptibility for changes depends more on the state of the artery and on exercise intensity, rather than the location