title: Suppressing inflammation by inhibiting the NF-κB pathway contributes to the neuroprotective effect of angiotensin-(1-7) in rats with permanent cerebral ischaemia.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors: Teng
authors: T
authors: Jiang
authors: Li
authors: L
authors: Gao
authors: Jun
authors: J
authors: Guo
authors: Jie
authors: J
authors: Lu
authors: Yao
authors: Y
authors: Wang
authors: Yingdong
authors: Y
authors: Zhang
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology / Q000627:therapeutic use*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors
chemical_list: C092006:7-Ala-angiotensin (1-7); D057912:Angiotensin II Type 2 Receptor Blockers; D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; C073402:PD 123319; D000803:Angiotensin I; C118790:angiotensin I (1-7)