title: Candesartan decreases the sympatho-adrenal and hormonal response to isolation stress.
abstract: A change from group housing to isolation in unfamiliar metabolic cages represents, for rodents, a significant emotional stress. We studied the effect of candesartan, a peripheral and central angiotensin II AT1-receptor antagonist, on the hormonal and sympathetic response to acute isolation. We pretreated rats with 1 mg/kg/day candesartan for 13 days via subcutaneously implanted osmotic minipumps, followed by 24-hour isolation in individual metabolic cages. We measured brain, pituitary and adrenal angiotensin II (Ang II) receptor binding by quantitative autoradiography and adrenal hormones and catecholamines by RIA and HPLC. Isolation increased adrenal catecholamines, aldosterone and corticosterone, AT1-receptor binding in the zona glomerulosa and AT2-receptor binding in the adrenal medulla. Candesartan pretreatment decreased adrenal catecholamines, aldosterone and corticosterone, AT1-receptor binding in adrenal zona glomerulosa and medulla, pituitary gland and the hypothalamic paraventricular nucleus, and AT2-receptor binding in adrenal medulla, but increased AT2-receptor binding in zona glomerulosa. We conclude that peripheral and central AT1-receptor blockade with candesartan decreases the sympatho-adrenal and hormonal response to acute stress. Our results indicate that Ang II is an important stress hormone and suggest that blockade of the physiologically active AT 1-receptors could influence stress-related disorders.
authors.affiliation: Section on Pharmacology, NIMH, NIH, Bethesda, MD 20892, USA, ArmandoI@intra.nimh.nih.gov, Centro de Investigaciones Endocrinologicas, CONICET, Buenos Aires, Argentina.
authors.forename: Ines
authors.initials: I
authors.lastname: Armando
authors.affiliation: Centro de Investigaciones Endocrinologicas, CONICET, Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carranza
authors.affiliation: Section on Pharmacology, NIMH, NIH, Bethesda, MD 20892, USA.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Centro de Investigaciones Endocrinologicas, CONICET, Buenos Aires, Argentina.
authors.forename: Marta
authors.initials: M
authors.lastname: Barontini
authors.affiliation: Section on Pharmacology, NIMH, NIH, Bethesda, MD 20892, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Section on Pharmacology, NIMH, NIH, Bethesda, MD 20892, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Saavedra
keywords: adrenal gland; angiotensin receptors; brain; catecholamines; corticoids; pituitary gland; renin-angiotensin system