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

• Main Authors: Qing-Guang Wang, Xiao Xue, Yang Yang, Peng-Yu Gong, Teng Jiang, Ying-Dong Zhang
• Format: Article
• Language: English
• Published: Hindawi - SAGE Publishing 2018-09-01
• Series: Journal of the Renin-Angiotensin-Aldosterone System
• Online Access: https://doi.org/10.1177/1470320318799587

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.