Cellular and Molecular Neurobiology

, Volume 32, Issue 5, pp 667–681

Angiotensin II AT1 Receptor Blockers Ameliorate Inflammatory Stress: A Beneficial Effect for the Treatment of Brain Disorders

Review Paper

DOI: 10.1007/s10571-011-9754-6

Cite this article as:
Saavedra, J.M. Cell Mol Neurobiol (2012) 32: 667. doi:10.1007/s10571-011-9754-6

Abstract

Excessive allostatic load as a consequence of deregulated brain inflammation participates in the development and progression of multiple brain diseases, including but not limited to mood and neurodegenerative disorders. Inhibition of the peripheral and brain Renin–Angiotensin System by systemic administration of Angiotensin II AT1 receptor blockers (ARBs) ameliorates inflammatory stress associated with hypertension, cold-restraint, and bacterial endotoxin administration. The mechanisms involved include: (a) decreased inflammatory factor production in peripheral organs and their release to the circulation; (b) reduced progression of peripherally induced inflammatory cascades in the cerebral vasculature and brain parenchyma; and (c) direct anti-inflammatory effects in cerebrovascular endothelial cells, microglia, and neurons. In addition, ARBs reduce bacterial endotoxin-induced anxiety and depression. Further pre-clinical experiments reveal that ARBs reduce brain inflammation, protect cognition in rodent models of Alzheimer’s disease, and diminish brain inflammation associated with genetic hypertension, ischemia, and stroke. The anti-inflammatory effects of ARBs have also been reported in circulating human monocytes. Clinical studies demonstrate that ARBs improve mood, significantly reduce cognitive decline after stroke, and ameliorate the progression of Alzheimer’s disease. ARBs are well-tolerated and extensively used to treat cardiovascular and metabolic disorders such as hypertension and diabetes, where inflammation is an integral pathogenic mechanism. We propose that including ARBs in a novel integrated approach for the treatment of brain disorders such as depression and Alzheimer’s disease may be of immediate translational relevance.

Keywords

Brain Renin–Angiotensin systemAngiotensin II AT1 receptor blockersStressBrain inflammationDepressionAnxietyMood disordersNeurodegenerative disordersAlzheimer’s diseaseStrokeCognition

Copyright information

© Springer Science+Business Media, LLC (outside the USA)  2011

Authors and Affiliations

  1. 1.Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental HealthNational Institutes of HealthBethesdaUSA