Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT1 receptor antagonists
Anxiety; Brain; Catecholamines; CRH; Inflammation; Stress
The brain and the peripheral (hormonal) angiotensin II systems are stimulated during stress. Activation of brain angiotensin II AT1 receptors is required for the stress-induced hormone secretion, including CRH, ACTH, corticoids and vasopressin, and for stimulation of the central sympathetic activity. Long-term peripheral administration of the angiotensin II AT 1 antagonist candesartan blocks not only peripheral but also brain AT1 receptors, prevents the hormonal and sympathoadrenal response to isolation stress and prevents the formation of stress-induced gastric ulcers. The mechanisms responsible for the prevention of stress-induced ulcers by the AT1 receptor antagonist include protection from the stress-induced ischemia and inflammation (neutrophil infiltration and increase in ICAM-1 and TNF-α) in the gastric mucosa and a partial blockade of the stress-induced sympathoadrenal stimulation, while the protective effect of the glucocorticoid release during stress is maintained. AT1 receptor antagonism prevents the stress-induced decrease in cortical CRH1 and benzodiazepine binding and is anxiolytic. Blockade of brain angiotensin II AT1 receptors offers a novel therapeutic opportunity for the treatment of anxiety and other stress-related disorders. © 2005 Elsevier B.V. All rights reserved.
Saavedra, J., Ando, H., Armando, I., Baiardi, G., Bregonzio, C., Juorio, A., & Macova, M. (2005). Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT1 receptor antagonists. Regulatory Peptides, 128 (3). http://dx.doi.org/10.1016/j.regpep.2004.12.015