Expression of angiotensin II and its receptors in the normal and hypoxic amoeboid microglial cells and murine BV-2 cells.

Involvement of the local angiotensin receptor system in the central nervous system is well documented, yet its cellular localization and role in the glial cells have remained elusive. This study reports expression of angiotensin II and its receptors namely, angiotensin II receptor type 1 (AT(1)) and angiotensin II receptor type 2 (AT(2)) in the amoeboid microglial cells in the neonatal rat brain. In rats subjected to hypoxia, the amount of angiotensin II released in the corpus callosal tissue was reduced as revealed by enzyme immunoassay. Expression of AT(1) mRNA and protein was down-regulated after hypoxic exposure, but AT(2) was up-regulated. In BV-2 cells exposed to hypoxia for 4 h, expression of AT(1) mRNA was reduced but AT(2) was increased. These changes were further intensified respectively in LPS-stimulated microglia. Edaravone enhanced AT(1) expression but suppressed AT(2) expression significantly in lipopolysaccharide-stimulated cells. Neutralization of AT(2) with its antiserum significantly increased mRNA expression of tumor necrosis factor-alpha and interleukin-1beta but decreased that of transforming growth factor-beta1. In conclusion, the present results suggest that AT(1) may be linked to regulation of vasodilation for increase of blood flow in hypoxic conditions, while up-regulated expression of AT(2) may reduce inflammatory responses through suppression of proinflammatory cytokines and elimination of free radicals.