Suppressing inflammation by inhibiting the NF-κB pathway contributes to the neuroprotective effect of angiotensin-(1-7) in rats with permanent cerebral ischaemia

Br J Pharmacol. 2012 Dec;167(7):1520-32. doi: 10.1111/j.1476-5381.2012.02105.x.


Background and purpose: Angiotensin-(1-7) [Ang-(1-7)] has anti-inflammatory effects in peripheral organs, but its effects in ischaemic stroke are unclear as yet. We investigated whether its anti-inflammatory effect contributes to the neuroprotection induced by Ang-(1-7) in a rat model of permanent middle cerebral artery occlusion (pMCAO).

Experimental approach: We infused Ang-(1-7), Mas receptor antagonist A-779, angiotensin II type 2 receptor antagonist PD123319 or artificial CSF into the right lateral ventricle of male Sprague-Dawley rats from 48 h before onset of pMCAO until the rats were killed. Twenty-four hours after pMCAO, the neuroprotective effect of Ang-(1-7) was analysed by evaluating infarct volume and neurological deficits. The levels of oxidative stress were detected by spectrophotometric assay. The activation of NF-κB was assessed by Western blot and immunohistochemistry analysis. The level of COX-2 was tested by Western blot analysis and concentrations of pro-inflammatory cytokines were measured by elisa.

Key results: Infusion of Ang-(1-7), i.c.v., significantly reduced infarct volume and improved neurological deficits. It decreased the levels of oxidative stress and suppressed NF-κB activity, which was accompanied by a reduction of pro-inflammatory cytokines and COX-2 in the peri-infarct regions. These effects of Ang-(1-7) were reversed by A-779 but not by PD123319. Additionally, infusion of A-779 alone increased oxidative stress levels and enhanced NF-κB activity, which was accompanied by an up-regulation of pro-inflammatory cytokines and COX-2.

Conclusion and implications: Our findings indicate that suppressing NF-κB dependent pathway via Mas receptor may represent one mechanism that contributes to the anti-inflammatory effects of Ang-(1-7) in rats with pMCAO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / pharmacology
  • Angiotensin I / therapeutic use*
  • Angiotensin II / analogs & derivatives
  • Angiotensin II / pharmacology
  • Angiotensin II Type 2 Receptor Blockers / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Behavior, Animal / drug effects
  • Cerebrovascular Circulation / drug effects
  • Imidazoles / pharmacology
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / physiopathology
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Male
  • NF-kappa B / antagonists & inhibitors*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Peptide Fragments / pharmacology
  • Peptide Fragments / therapeutic use*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / antagonists & inhibitors


  • 7-Ala-angiotensin (1-7)
  • Angiotensin II Type 2 Receptor Blockers
  • Anti-Inflammatory Agents
  • Imidazoles
  • NF-kappa B
  • Neuroprotective Agents
  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Pyridines
  • Receptors, G-Protein-Coupled
  • Angiotensin II
  • PD 123319
  • Angiotensin I
  • angiotensin I (1-7)