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Angiotensin II AT1 Receptor Blockade Prolongs the Lifespan of Spontaneously Hypertensive Rats and Reduces Stress-Induced Release of Catecholamines, Glucocorticoids, and Vasopressin

Authors

  • GUSTAVO BAIARDI,

    Corresponding author
    1. Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
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  • CLAUDIA BREGONZIO,

    1. Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
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  • MIROSLAVA JEZOVA,

    1. Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
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  • INES ARMANDO,

    1. Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
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  • JUAN M. SAAVEDRA

    1. Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
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Address for correspondence: Gustavo Baiardi, Ph.D., Section on Pharmacology, DIRP, NIMH, NIH, DHHS, 10 Center Drive, Bldg. 10, Room 2D-57, Bethesda, MD 20892, USA. Voice: 301-451-8377; fax: 301-402-0337. e-mail: baiardig@intra.nimh.nih.gov

Abstract

Abstract: A 2-week pretreatment with an Angiotensin II AT1 antagonist prevented the adrenomedullary and hormonal response to isolation stress. We studied the effect of life-long treatment with the AT1 receptor antagonist candesartan, 10 mg/kg/day, or vehicle administered orally in the drinking water from 8 weeks of age on the response to stress of stress-sensitive spontaneously hypertensive rats (SHRs) and their normotensive controls, the Wistar Kyoto (WKY). Rats were submitted to 24-h isolation stress at different times during the treatment. Treatment with candesartan extended the lifespan of SHRs. AT1 receptor blockade retained its capacity to blunt the response to isolation stress over a long period of treatment. The AT1 antagonist inhibited epinephrine release in SHR but not in WKY rats during the first 3 months, corticosterone release in SHR and WKY rats during 10 months, and vasopressin release in SHR rats during 18 months of treatment when rats were submitted to isolation stress. There were no changes in vasopressin release in WKY rats during stress or after AT1 receptor blockade. We conclude that the blockade of the stress response by the AT1 receptor antagonist is long lasting and differs between stress-prone SHR and WKY rats and that the specific components of the stress response (sympathoadrenal activity, hypothalamic-pituitary-adrenal axis activation, and vasopressin release) react differently to AT1 receptor blockade. The long-term protective effects of AT1 receptor blockade can be important in animals vulnerable to stress and, in conjunction with the normalization of blood pressure, can prolong lifespan through end-organ protection.

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