The Angiotensin II AT 1 receptor blockade inhibits the lipopolysaccharide‐induced inflammatory response in the nucleus tractus solitarii (NTS)

Systemic administration of an Angiotensin II AT 1 receptor blocker (ARB) inhibited the lipopolysaccharide (LPS)‐induced pro‐inflammatory reaction in periphery. LPS‐induced immune‐brain communication promotes anxiety and sickness behavior. These behavioral changes have been strongly linked to vagal stimulation by circulating cytokines. The main recipient of vagal afferents in the brainstem is the nucleus tractus solitarii (NTS), which expresses a large number of AT 1 receptors, both in somata and in terminals (from the nodose ganglia). We explore the role of the AT 1 receptors on the LPS‐induced inflammatory response in the NTS. LPS (ip, 50 μg/kg, 3h) increased the NTS gene expression of the pro‐inflammatory factors IL‐6, COX‐2, iNOS and ICAM‐1; stimulated the early transcription factors c‐Fos and NF‐κB; augmented the expression of tyrosine hydroxylase (TH); and enhanced the LPS co‐receptor CD14 expression. LPS did not affect the AT 1 receptor expression. The administration of the ARB candesartan (sc, 1 mg/kg/d, 3d before LPS) reduced the LPS‐induced gene expression of all pro‐inflammatory components measured; and that of IκB‐α and c‐Fos. Candesartan also reduced TH expression and CD14 gene expression and it did not affect the AT 1 receptor. ARBs reduced the pro‐inflammatory gene expression response to LPS in the brain. This might be translated into reduction of LPS‐induced behavioral changes.