Brain and peripheral angiotensin II play a major role in stress

Abstract

Angiotensin II (Ang II), the active principle of the renin-angiotensin system (RAS), was discovered as a vasoconstrictive, fluid retentive circulating hormone. It was revealed later that there are local RAS in many organs, including the brain. The physiological receptor for Ang II, the AT₁ receptor type, was found to be highly expressed in many tissues and brain areas involved in the hypothalamic-pituitary-adrenal axis response to stress and in the sympathoadrenal system. The production of circulating and local Ang II, and the expression of AT₁ receptors increase during stress. Blockade of peripheral and brain AT₁ receptors with receptor antagonists administered peripherally prevented the hormonal and sympathoadrenal response to isolation stress, the stress-related alterations in cortical CRF₁ and benzodiazepine receptors, part of the GABA_A complex, and reduced anxiety in rodents. AT₁ receptor blockade prevented the ulcerations of the gastric mucosa produced by cold-restraint stress, by preservation of the gastric blood flow, prevention of the stress-induced inflammatory response of the gastric mucosa, and partial blockade of the sympathoadrenal response to the stress. Our observations demonstrate that Ang II is an important stress hormone, and that blockade of AT₁ receptors could be proposed as a potentially useful therapy for stress-induced disorders.

• Angiotensin receptor types
• candesartan
• cold-restraint stress
• hypothalamic-pituitary-adrenal axis
• isolation stress
• paraventricular nucleus