Key result
Central infusion of Ang IV dose-dependently suppressed the expression of pro-inflammatory cytokines in the brains of rats with chronic cerebral hypoperfusion.
Why the study?
Does central infusion of Angiotensin IV suppress inflammation and neuropathological changes in rats with chronic cerebral hypoperfusion?
Does central infusion of Angiotensin IV suppress inflammation and neuropathological changes in rats with chronic cerebral hypoperfusion?
Central infusion of Angiotensin IV suppresses brain inflammation via the AT4 receptor in a rat model of chronic cerebral hypoperfusion, independent of systemic blood pressure.
Extends preclinical evidence for central Ang IV effects; does not support clinical use in 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.
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Wang et al. (2018) studied chronic cerebral hypoperfusion. central angiotensin IV (Ang IV) infusion vs. artificial cerebrospinal fluid or divalinal-Ang IV was evaluated on levels of Aβ 42, p-tau and pro-inflammatory cytokines in the brain. Central infusion of Ang IV dose-dependently suppressed the expression of pro-inflammatory cytokines in the brains of rats with chronic cerebral hypoperfusion.
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