Angiotensin IV suppresses inflammation in the brains of rats with chronic cerebral hypoperfusion

INTRODUCTION: This study aimed to evaluate the influence of central angiotensin IV (Ang IV) infusion on chronic cerebral hypoperfusion (CCH)-related neuropathological changes including amyloid-β (Aβ), hyperphosphorylated tau (p-tau) and the inflammatory response. MATERIALS AND METHODS: Rats with CCH received central infusion of Ang IV, its receptor AT(4)R antagonist divalinal-Ang IV or artificial cerebrospinal fluid for six weeks. During this procedure, the systolic blood pressure (SBP) was monitored, and the levels of Aβ(42), p-tau and pro-inflammatory cytokines in the brain were detected. RESULTS: Rats with CCH exhibited higher levels of Aβ(42), p-tau and pro-inflammatory cytokines in the brain when compared with controls. Infusion of Ang IV significantly reduced the expression of pro-inflammatory cytokines in the brains of rats with CCH. Meanwhile, the reduction of pro-inflammatory cytokines levels caused by Ang IV was reversed by divalinal-Ang IV. During the treatment, the SBP in rats was not significantly altered. CONCLUSION: This study demonstrates for the first time that Ang IV dose-dependently suppresses inflammation through AT(4)R in the brains of rats with CCH, which is independent from SBP. These findings suggest that Ang IV/AT(4)R may represent a potential therapeutic target for CCH-related neurological diseases.