RESUMO
Vasopressin and CRH have complementary roles in the secretion of ACTH following different stress modalities. The concomitant use of V1b and CRF1 receptor antagonists completely inhibits ACTH secretion in response to different stress modalities. The combination of the CRF1 antagonist SSR125543 with the V1b antagonist SSR149415 effectively suppressed plasma ACTH 1.30 h after injection in rats stressed by ether vapor inhalation for 1 min, restraint stress for 1 h or forced swimming for 5 min. The duration of the effect was also studied. The CRF1 antagonist effectively suppressed ACTH secretion in restraint stress, while the V1b antagonist was effective against ether inhalation. Both antagonists were necessary to block the forced swimming stress response. SSR125543 induced a prolonged effect and can be used in a model of prolonged HPA axis blockade.
Assuntos
Hormônio Adrenocorticotrópico/efeitos dos fármacos , Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacologia , Hormônio Liberador da Corticotropina/efeitos dos fármacos , Hidrocarbonetos Halogenados/farmacologia , Indóis/farmacologia , Pirrolidinas/farmacologia , Estresse Psicológico/metabolismo , Tiazinas/farmacologia , Vasopressinas/efeitos dos fármacos , Administração por Inalação , Hormônio Adrenocorticotrópico/metabolismo , Anestésicos Inalatórios/farmacologia , Animais , Hormônio Liberador da Corticotropina/metabolismo , Éter/farmacologia , Sistema Hipotálamo-Hipofisário , Masculino , Modelos Animais , Sistema Hipófise-Suprarrenal , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Receptores de Vasopressinas/metabolismo , Restrição Física , Natação , Vasopressinas/metabolismoRESUMO
Predominantly emotional stressors activate a wide range of brain areas, as revealed by the expression of immediate early genes, such as c-fos. Chlorella vulgaris (CV) is considered a biological response modifier, as demonstrated by its protective activities against infections, tumors and stress. We evaluated the effect of acute pretreatment with CV on the peripheral and central responses to forced swimming stress in adult male rats. Pretreatment with CV produced a significant reduction of stress-related hypothalamic-pituitary-adrenal activation, demonstrated by decreased corticotrophin releasing factor gene expression in the hypothalamic paraventricular nucleus (PVN) and lower ACTH response. Hyperglycemia induced by the stressor was similarly reduced. This attenuated neuroendocrine response to stress occurred in parallel with a diminished c-fos expression in most evaluated areas, including the PVN. The data presented in this study reinforce the usefulness of CV to diminish the impact of stressors, by reducing the HPA response. Although our results suggest a central effect of CV, further studies are necessary to understand the precise mechanisms underpinning this effect.