Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT1 receptor antagonists.
The brain and the peripheral (hormonal) angiotensin II systems are stimulated during stress. Activation of brain angiotensin II AT(1) 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 AT(1) 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 AT(1) receptor antagonist include protection from the stress-induced ischemia and inflammation (neutrophil infiltration and increase in ICAM-1 and TNF-alpha) 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. AT(1) receptor antagonism prevents the stress-induced decrease in cortical CRH(1) and benzodiazepine binding and is anxiolytic. Blockade of brain angiotensin II AT(1) receptors offers a novel therapeutic opportunity for the treatment of anxiety and other stress-related disorders.
Saavedra
Juan M
JM
Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-1514, USA. Saavedrj@mail.nih.gov
Ando
Hiromichi
H
Armando
Inés
I
Baiardi
Gustavo
G
Bregonzio
Claudia
C
Juorio
Augusto
A
Macova
Miroslava
M
D000804:Angiotensin II / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001921:Brain / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D013315:Stress, Psychological / Q000517:prevention & control*
D047228:Angiotensin II Type 1 Receptor Blockers; D014151:Anti-Anxiety Agents; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II