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Abstract-The clinical efficacy of exercise training in individuals with heart failure is well established, but the mechanism underlying such efficacy has remained unclear. An imbalance between cardiac hypertrophy and angiogenesis is implicated in the transition to heart failure. We investigated the effects of exercise training on cardiac pathophysiology in hypertensive rats. Dahl salt-sensitive rats fed a high-salt diet from 6 weeks of age were assigned to sedentary or exercise (swimming)-trained groups at 9 weeks. Exercise training attenuated the development of heart failure and increased survival, without affecting blood pressure, at 18 weeks. It also attenuated left ventricular concentricity without a reduction in left ventricular mass or impairment of cardiac function. Interstitial fibrosis was increased and myocardial capillary density was decreased in the heart of sedentary rats, and these effects were attenuated by exercise. Exercise potentiated increases in the phosphorylation of Akt and mammalian target of rapamycin observed in the heart of sedentary rats, whereas it inhibited the downregulation of proangiogenic gene expression apparent in these animals. The abundance of the p110␣ isoform of phosphatidylinositol 3-kinase was decreased, whereas those of the p110␥ isoform of phosphatidylinositol 3-kinase and the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase were increased, in the heart of sedentary rats, and all of these effects were prevented by exercise. Thus, exercise training had a beneficial effect on cardiac remodeling and attenuated heart failure in hypertensive rats, with these effects likely being attributable to the attenuation of left ventricular concentricity and restoration of coronary angiogenesis through activation of phosphatidylinositol 3-kinase ( Key Words: hypertension Ⅲ sodium-dependent Ⅲ heart failure Ⅲ exercise Ⅲ hypertrophy Ⅲ rats Ⅲ Dahl Ⅲ coronary angiogenesis .H eart failure is a final common consequence of various forms of heart disease and is a leading cause of mortality worldwide. Cardiac hypertrophy associated with pathological conditions such as hypertension, myocardial infarction, and valvular heart disease has been thought to be an adaptive response to increased external load, given that it can result in normalization of the increase in wall stress induced by mechanical overload. However, increased cardiac mass is also associated with increased morbidity and mortality, 1 with sustained overload eventually leading to heart failure.The serine-threonine protein kinase Akt is an important mediator of phosphatidylinositol 3-kinase (PI3K) signaling and regulates multiple cellular functions. 2 PI3K-Akt signaling is implicated in the regulation of cardiac growth, contractile function, and coronary angiogenesis. [3][4][5] A mismatch between the number of coronary capillaries and the size of cardiomyocytes, resulting in myocardial hypoxia, is thought to develop during the progression of cardiac hypertrophy. 6 Indeed, studies have in...

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Long-term administration of pioglitazone attenuated left ventricular hypertrophy and fibrosis as well as inhibited phosphorylation of mammalian target of rapamycin and p70S6 kinase in the heart of hypertensive rats. The beneficial cardiac effects of pioglitazone are likely attributable, at least partly, both to the activation of AMP-activated protein kinase signaling through stimulation of adiponectin secretion and to the inhibition of Akt signaling.