The influence of sirtuins on beta 2 adrenergic pathway in heart of rats submitted to stress

Abstract

Understanding the mechanisms related to stress response occupies the attention of scientists and clinicians since the definition of the term stress by the endocrinologist Hans Selye in 1936. It is believed that at least one third of the diseases that lead people to seek medical care are related to stress. The current conditions of life in the world represent a major cause of stress in humans, the called psychosocial stress, caused by the accelerated process of urbanization and changing lifestyles. The endocrine stress response in humans and animals includes the activation of the hypothalamic-pituitary-adrenal (HPA), which stimulates the secretion of glucocorticoids by the adrenal cortex, and activation of the sympathetic nervous system-adrenal medulla that stimulates the release of catecholamines. The activation of the sympathetic nervous system (SNS) and the HPA axis during the stress response promotes the over stimulation of beta adrenergic receptors (beta-ARs) causing a change in the ratio beta 1/beta 2-AR in cardiomyocytes. This change happens in both animal model and in human heart failure, may indicate the important role of beta 2-AR signaling in cardiac diseases. Recent evidence demonstrates an overlap of the effectors mechanisms of beta 2-AR-Gi and sirtuins, especially SIRT1 and SIRT3, through the PI3K-Akt pathway. In this study we aimed to evaluate the role of sirtuins on the beta 2-AR signaling in cardiac tissue of rats submitted to foot-shock stress. Rats submitted to foot-shock stress have been used as experimental models to investigate adaptive mechanisms mainly in the cardiovascular system. The foot-shock animal model is able to demonstrate the effect of stress on the cardiac beta-ARs by increasing beta 2-AR protein expression. Thus, it is of fundamental importance to investigate cardiac function in animals submitted to foot-shock stress, and the molecular mechanisms involved in beta 2-AR signaling in the heart. Therefore, the study of the role of sirtuins in the intracellular responses of beta 2-AR signaling may help to understand the post-stress adrenergic remodeling and its consequence in the prognosis of cardiac events. (AU)