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

Abstract

Understanding the mechanisms related to the stress response occupies the attention of scientists and clinicians since its definition by the endocrinologist Hans Selye in 1936. It is now accepted 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 unhealthy lifestyles. The endocrine stress response in humans and animals includes the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which increases the secretion of glucocorticoids by the adrenal cortex, and activation of the sympathetic nervous system-adrenal medulla that releases 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 (²-ARs) causing a change in the ratio ²1/²2-AR in the heart by increasing ²2-AR protein expression. This change has been described in both animal model and in human heart failure, and may indicate the important role of ²2-AR signaling in cardiac diseases. Recent evidence demonstrates an overlap of the effectors mechanisms of ²2-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 ²2-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 heart. This experimental model may help to clarify some mechanisms underlying cardiac function involved in ²2-AR signaling in the heart and the role-played by sirloins in this scenario. Therefore, it may also contribute to understand the post-stress adrenergic remodeling and its consequence in the prognosis of cardiac events. (AU)