Angiotensin receptor blockers for bipolar disorder

Abstract

Studies have suggested that the brain renin angiotensin system (RAS) regulates cerebral flow, autonomic and hormonal systems, stress, innate immune response and behavior, being implicated in several brain disorders such as major depression, Parkinson’s and Alzheimer’s disease. The angiotensin II receptor subtype 1 (AT1R) is distributed in brain regions responsible for the control of stress response through peripheral and central sympathetic hyperactivation as well as in the hypothalamic paraventricular region, areas known for the release of several neurotransmitters related to inflammatory response facilitation. This relationship leads to the assumption that AT1R might be the receptor most related to the central deleterious actions of angiotensin II. New evidences from clinical studies have shown a possible role for RAS in the pathogenesis of bipolar disorder (BD), a multifactorial disorder with acknowledged presence of neuronal damage via oxidative stress in brain areas such as hippocampus, prefrontal cortex and striatum. Given the studies highlighting AT1R activation as a central pro-inflammatory pathway and, conversely, the involvement of inflammatory response in the pathogenesis of BD; this paper hypothesizes the use of AT1R antagonists for BD management and prevention of its neuroprogression, due to their anti-inflammatory and neuroprotective effects.