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 ATR 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, p-tau and pro-inflammatory cytokines in the brain were detected.

RESULTS

Rats with CCH exhibited higher levels of Aβ, 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 ATR in the brains of rats with CCH, which is independent from SBP. These findings suggest that Ang IV/ATR may represent a potential therapeutic target for CCH-related neurological diseases.