Avaliação do impacto do estresse crônico imprevisível sobre componentes do sistema renina-angiotensina no hipotálamo

Abstract

Stress is characterized as everything that threatens the balance of an organism, requiring a response from the individual to neutralize it. When the stimulus is persistent, very intense or there is an inability to activate the adaptation systems, it can lead to the development of cardiovascular disorders (arterial hypertension, cardiac arrhythmia, sympathetic hyperactivation, among others) and neuropsychiatric disorders (mood and anxiety disorders, etc.). Among the physiological components triggered by the stress response, the activation of the sympathetic-adrenal and hypothalamic-pituitary-adrenal (HPA) axes stands out. In addition to the canonical neurohumoral pathways, there are other biological systems related to the stress response, including the renin-angiotensin system (RAS), which has been extensively studied, especially in acute stress. This work aimed evaluate the impact of a murine model of chronic unpredictable stress (CUS) on the expression of RAS components in the hypothalamus. C57BL/6J mice were randomly subjected to various stressors (eg, water deprivation, exposure to stroboscopic light, social isolation etc.), for three consecutive weeks. Then, the biochemical, cardiovascular, morphological and behavioral parameters were analyzed and compared with a control group. The results indicate that the proposed and developed protocol was efficient in inducing chronic stress, since the animals submitted to ECI showed increased levels of corticosterone, adrenal gland hypertrophy, tachycardia, anxiety-like behavior, depressive-like behavior, reduction of BDNF levels in the prefrontal cortex, hippocampus, and hypothalamus and, curiously, decreases in fear memory expression behavior. Furthermore, interestingly, the CUS animals showed increased AT1 receptor gene expression and reduced Mas receptor expression in the hypothalamus. Therefore, it is concluded that the experimental animals, after three weeks of exposure to various stressors, showed physiological, morphological and behavioral responses typical of chronically stressed animals, in addition to changes in RAS components in the hypothalamus. Therefore, the standardized protocol is efficient for the study of chronic stress and its consequences, enabling the development of new research with possible strategies to mitigate the effects of chronic stress, such as directed to the cerebral RAS.