Figure 8.
Angiotensin II and inflammatory signal pathways in the brain. AT1 receptor activity is an important factor during brain inflammation. Angiotensin II and inflammatory stimuli interact, enhancing several common downstream signaling pathways. ARBs reduce inflammatory induction of peripheral cytokines and their release to the circulation (1). Inflammatory signals (1) induce transcription of angiotensin II AT1, CD14, cytokine, and EP4 receptors in brain target cells (2). Angiotensin II AT1 receptor blockade eliminates angiotensin II-stimulated downstream signaling and represses downstream transcription factors NF-κB and AP-1 (3). This limits inflammation-induced increase in brain inflammatory cascades: proinflammatory cytokines, cytokine and prostanoid receptors, inducible enzymes leading to PGE2 and NO overproduction and adhesion molecules (4). In turn, this reduces microglia activation and neuronal injury in brain parenchyma (5) limiting the brain inflammatory reaction.