Peripheral administration of an angiotensin II AT1 receptor antagonist decreases the hypothalamic-pituitary-adrenal response to isolation stress
Angiotensin II, which stimulates AT1 receptors, is a brain and peripheral stress hormone. We pretreated rats with the AT1 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 AT1 receptor binding in hypothalamic paraventricular nucleus as well as anterior pituitary ACTH, and decreased posterior pituitary AVP. Isolation stress also increased AT1 receptor binding and AT1B mRNA in zona glomerulosa and AT2 binding in adrenal medulla, adrenal catecholamines, tyrosine hydroxylase mRNA, aldosterone, and corticosterone. Candesartan blocked AT1 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 AT2 binding in adrenal medulla; and substantially decreased urinary AVP, corticosterone, aldosterone, and catecholamines during isolation. Peripheral pre-treatment with an AT1 receptor antagonist blocks brain and peripheral AT1 receptors and inhibits the hypothalamic-pituitary-adrenal response to stress, suggesting a physiological role for peripheral and brain AT1 receptors during stress and a possible beneficial effect of AT1 antagonism in stress-related disorders.
Armando, I., Carranza, A., Nishimura, Y., Hoe, K., Barontini, M., Terrón, J., Falcón-Neri, A., Ito, T., Juorio, A., & Saavedra, J. (2001). Peripheral administration of an angiotensin II AT1 receptor antagonist decreases the hypothalamic-pituitary-adrenal response to isolation stress. Endocrinology, 142 (9). http://dx.doi.org/10.1210/endo.142.9.8366