Brain renin-angiotensin system in the injured brain: The role of astrocytes and microglia

ALBERTO J. RAMOS

Angiotensin in Health and Disease

Elsevier

Año: 2022;

Renin-angiotensin system (RAS) is a well described homeostatic signaling pathway that controls blood pressure and modify ionic balance by releasing active molecules derived from angiotensinogen produced in the liver and circulating in the blood. In recent decades components of a regional RAS have been discovered in the brain. The presence of a blood-brain barrier maintains this brain RAS isolated from the rest of the body, requiring local synthesis of the substrates, metabolites and enzymes. Astrocytes, the main homeostatic cell in the Central Nervous System (CNS), is the source of angiotensinogen which is the initialsubstrate for the brain RAS. On the other hand, angiotensin receptors AT1R and AT2R have been described in neuronal populations of the cardiovascular centers of the CNS, but there is some controversy about their expression in astrocytes and microglia. However, angiotensin II infusion or blockage of angiotensin receptors induces remarkable alterations in the pro-inflammatory status of reactive astrocytes and microglia, being the activation of AT1R pro-inflammatory and AT2R anti-inflammatory. Pathologically remodeled astrocytes with pro-inflammatory gain of function are cells capable of inducing neuronal death andBBB disruption and therefore over-activation of AT1R-driven pathways may havedeleterious consequences not only in hypertension but also in acute CNS damage or in neurodegenerative diseases. In this chapter, the main findings about the brain RAS findings are discussed, and three different models for angiotensin actions on glial cells are proposed. The present physiological model for brain RAS proposes that all components of the brain RAS are not synthesized by the same cell type and therefore this system requires a profound interaction among CNS cell types that is still not completely understood. Finally, the potential beneficial effect of pharmacological agents acting on the brain RAS in neurodegenerative diseases is commented.