Poor adaptation to stress, alterations in cerebrovascular function and excessive
brain inflammation play critical roles in the pathophysiology of many psychiatric and
neurological disorders such as major depression,
schizophrenia,
post traumatic stress disorder, Parkinson's and
Alzheimer's diseases and
traumatic brain injury. Treatment for these highly prevalent and devastating conditions is at present very limited and many times inefficient, and the search for novel therapeutic options is of major importance. Recently, attention has been focused on the role of a brain regulatory
peptide,
Angiotensin II, and in the translational value of the blockade of its physiological AT(1) receptors. In addition to its well-known cardiovascular effects,
Angiotensin II, through AT(1) receptor stimulation, is a pleiotropic brain modulatory factor involved in the control of the reaction to stress, in the regulation of cerebrovascular flow and the response to
inflammation. Excessive brain AT(1) receptor activity is associated with exaggerated sympathetic and hormonal response to stress, vulnerability to cerebrovascular
ischemia and
brain inflammation, processes leading to neuronal injury. In animal models, inhibition of brain AT(1) receptor activity with systemically administered
Angiotensin II receptor blockers is neuroprotective; it reduces exaggerated stress responses and anxiety, prevents stress-induced gastric ulcerations, decreases vulnerability to
ischemia and
stroke, reverses chronic cerebrovascular
inflammation, and reduces acute inflammatory responses produced by bacterial
endotoxin. These effects protect neurons from injury and contribute to increase the lifespan.
Angiotensin II receptor blockers are compounds with a good margin of safety widely used in the treatment of
hypertension and their anti-inflammatory and vascular protective effects contribute to reduce renal and cardiovascular failure. Inhibition of brain AT(1) receptors in humans is also neuroprotective, reducing the incidence of
stroke, improving cognition and decreasing the progression of
Alzheimer's disease. Blockade of AT(1) receptors offers a novel and safe therapeutic approach for the treatment of illnesses of increasing prevalence and socioeconomic impact, such as
mood disorders and
neurodegenerative diseases of the brain.