A studied demonstrated that under norepinephrine effects, the heart suffers hypertrophy, especially on the left ventricle. In addition, there is a raised levels of atrial natriuretic peptide, higher expression of collagen I and III and interstitial fibrosis. 11 Characteristically, catecholamines enhance the stimulus to oxidative Abstract Physical activity is an important tool to interfere on the natural course of cardiac hypertrophy to heart failure and also to manage this condition once it is established. Aerobic physical activity increases parasympathetic tone while decreases sympathetic activity. This scenario decreases peripheral vascular resistance, alters autonomic nervous system and affect cardiac effort and output. Moreover, exercise increases concentrations of Vascular Endothelial Growth Factor (VEGF) and Brain-derived Neurotrophic Factor (BDNF) on the brain, leading to cerebral vasculature changes, increased neuronal density and enhanced synapses strengthen. In addition, it promotes structural and functional changes on the cardiovascular system and brain. Exercise is widely shown to act on the prefrontal cortex and amygdala functions, which are related to autonomic nervous system, building a feedback system, linking central and peripheral tissues.Citation: Rêgo MLM, Cabral DAR. Hypertrophy, heart failure, brain and physical activity -the molecular basis of this connection. J Cardiol Curr Res.Citation: Rêgo MLM, Cabral DAR. Hypertrophy, heart failure, brain and physical activity -the molecular basis of this connection. J Cardiol Curr Res.nervous system, hemodynamic and molecular patterns -to explain HF and physical exercise effects to the brain.