We have demonstrated that Angiotensin II, through stimulation of AT1 receptors, contributes to regulate cerebral blood flow and participates in the control of the central and peripheral reactions to stress. Peripheral administration of AT1 antagonists blocks not only peripheral but also brain AT1 receptors. We have found that previous administration of Angiotensin II AT1 receptor antagonists decreases brain edema and stroke volume by 50% in genetically hypertensive rats after temporal occlusion of the middle cerebral artery with reperfusion. In rats submitted to acute isolation stress, similar administration of AT1 antagonists significantly decreases adrenaline, noradrenaline, vasopressin and ACTH release, evidence of an inhibition of the sympathoadrenal and pituitary response to stress. These results indicate that administration of AT1 antagonists could be therapeutically useful for the prevention and treatment of brain ischemia and stress-related disorders. When comparable doses are used, AT1 antagonists are more effective in reducing brain ischemia than ACE inhibitors or calcium channel blockers. In addition, AT1 antagonists produce a modest, but consistent and significant, reduction in weight gain, when administered prior either to stress or brain ischemia. This indicates that the AT1 antagonists have multiple sites of action and sympatholytic effects with therapeutic potential in stress and brain ischemia - Brain. Stress. Cerebrovascular flow. Rats. gerbils. mice. Stroke. In situ hybridization. Cloning.