RESUMO
Angiotensin II, which stimulates AT(1) receptors, is a brain and peripheral stress hormone. We pretreated rats with the AT(1) receptor antagonist candesartan for 13 d via sc-implanted osmotic minipumps, followed by 24-h isolation in individual metabolic cages. We measured angiotensin II receptor-type binding and mRNAs and tyrosine hydroxylase mRNA by quantitative autoradiography and in situ hybridization, catecholamines by HPLC, and hormones by RIA. Isolation increased AT(1) receptor binding in hypothalamic paraventricular nucleus as well as anterior pituitary ACTH, and decreased posterior pituitary AVP. Isolation stress also increased AT(1) receptor binding and AT(1B) mRNA in zona glomerulosa and AT(2) binding in adrenal medulla, adrenal catecholamines, tyrosine hydroxylase mRNA, aldosterone, and corticosterone. Candesartan blocked AT(1) binding in paraventricular nucleus and adrenal gland; prevented the isolation-induced alterations in pituitary ACTH and AVP and in adrenal corticosterone, aldosterone, and catecholamines; abolished the increase in AT(2) binding in adrenal medulla; and substantially decreased urinary AVP, corticosterone, aldosterone, and catecholamines during isolation. Peripheral pretreatment with an AT(1) receptor antagonist blocks brain and peripheral AT(1) receptors and inhibits the hypothalamic-pituitary-adrenal response to stress, suggesting a physiological role for peripheral and brain AT(1) receptors during stress and a possible beneficial effect of AT(1) antagonism in stress-related disorders.
Assuntos
Antagonistas de Receptores de Angiotensina , Benzimidazóis/farmacologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Isolamento Social/psicologia , Estresse Psicológico/fisiopatologia , Tetrazóis/farmacologia , Corticosteroides/metabolismo , Glândulas Suprarrenais/metabolismo , Animais , Compostos de Bifenilo , Encéfalo/metabolismo , Catecolaminas/metabolismo , Catecolaminas/urina , Hormônios/urina , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Bombas de Infusão , Injeções Subcutâneas , Masculino , Hormônios Hipofisários/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Receptores de Angiotensina/metabolismo , Tirosina 3-Mono-Oxigenase/genéticaRESUMO
1. Dopamine was found in the tortoise brain; the highest concentration (3.7 mug/g) occurred in a region of the telencephalon containing the nucleus basalis and cortex olfactoria. This region may be considered similar to the mammalian and avian corpus striatum with respect to dopamine.2. The administration of reserpine or prenylamine substantially decreased the concentration of dopamine in the tortoise brain. This effect appeared later and lasted longer than in birds or mammals. When these drugs were given in doses which nearly depleted brain dopamine the characteristic signs observed in birds or mammals were not present.