Abstract 3197: Exercise Training Alters Left Ventricular Geometry and Improves Heart Failure in Dahl Salt-Sensitive Hypertensive Rats: Role of PI3K p110α/γ-Akt-mTOR-Mediated Activation of Proangiogenic Signaling
The clinical efficacy of exercise training in individuals with heart failure is well established. However, the mechanism underlying such efficacy remained unclear. Disruption of the balance between cardiac hypertrophy and angiogenesis is thought to contribute to the transition to heart failure. We investigated the effects of exercise training on cardiac pathophysiology in rats with salt-sensitive hypertension. Dahl salt-sensitive (DS) rats fed a high-salt diet from 6 weeks of age were assigned to sedentary (n=12) or exercise-trained (n=7) groups at 9 weeks. Exercise consisted of swimming for 1 hour per day on 5 days per week for 9 weeks. Exercise training attenuated the development of heart failure and increased survival without an effect on blood pressure. It also induced a shift from concentric to eccentric cardiac hypertrophy without impairing cardiac function. Marked interstitial fibrosis was detected in the heart of sedentary rats compared with that of age-matched controls (n=6); this increase in cardiac fibrosis was significantly attenuated by exercise. Myocardial capillary density was reduced in sedentary rats and this change was prevented by exercise. Exercise potentiated the increases in the phosphorylation of Akt and mammalian target of rapamycin observed in sedentary rat hearts, whereas it prevented the downregulation of hypoxia-inducible factor-1α, vascular endothelial growth factor, and endothelial nitric oxide synthase gene expression apparent in these animals. The phosphorylation of p70S6 kinase was increased in the heart of sedentary rats, but it was not affected further by exercise training. The abundance of p110α isoform of phosphoinositide 3-kinase protein was decreased whereas that of p110γ isoform and phosphorylation of ERK1/2 and p38 MAPK were increased in sedentary rat hearts, and all these effects were prevented by exercise. The present results show that exercise training had a beneficial effect on cardiac remodeling and attenuated heart failure in hypertensive DS rats. The attenuation of heart failure by exercise was likely attributable to the induction of physiological cardiac growth and coronary angiogenesis in a manner dependent on PI3K p110α/γ-Akt-mTOR signaling.