Science, Medicine, and the Anesthesiologist

Author: Charles Emala, M.D.

Anesthesiology July 2024, Vol. 141, A13–A15.

The peripheral renin angiotensin system (RAS) is a well-characterized hormonal system classically understood to regulate cardiovascular and renal functions, but evidence suggests that a central RAS regulates cognitive and emotional functions as well as neurologic disorders such as posttraumatic stress disorder (PTSD), depression, and Alzheimer’s disease. Prior clinical studies suggested that chronic treatment with angiotensin II type 1 receptors (AT1Rs) antagonists may attenuate memory decline in Alzheimer’s and, in some studies, reduce symptoms in PTSD. However, an incomplete understanding of the regional and network distribution of AT1Rs with correlations to behaviors and linkage to other central neurotransmitters currently limits potential therapeutic targeting of the central RAS for cognitive and behavioral disorders. This study combined mapping of AT1R gene expression from donor brains with specific brain regions linked to behaviors in a large functional magnetic resonance imaging (fMRI) data set (Neurosynth) with fMRIs obtained in the presence of AT1R antagonism (losartan) in 66 human subjects. This identified the regional distribution of AT1Rs and linked their expression to brain regions involved in memory, stress, reward, and motivational activities, and further linked their expression to other neurotransmitter signaling pathways including those modulated by dopamine, opioids, acetylcholine, and corticotropin-releasing hormone.

Take home message: The central RAS is primarily modulated by expression of the angiotensin II type 1 receptor in discrete brain regions linked to functions of memory, stress, reward, and motivation likely through modulation with other classic central neurotransmitters. A more complete understanding of the central RAS holds promise for therapeutic targeting of an array of disorders associated with memory, stress, and emotional disorders.