title: Effects of the angiotensin-(1-7)/Mas/PI3K/Akt/nitric oxide axis and the possible role of atrial natriuretic peptide in an acute atrial tachycardia canine model.
abstract: OBJECTIVE
  To investigate the effects of the angiotensin-(1-7) signaling pathway and the possible role of atrial natriuretic peptide (ANP) on atrial electrical remodeling in canines with acute atrial tachycardia.
  
  
  METHODS
  Forty dogs were randomly assigned to eight groups (five dogs/group): sham, paced control, paced + angiotensin-(1-7), paced + angiotensin-(1-7) + Mas inhibitor, paced + angiotensin-(1-7) + Akt inhibitor, paced + angiotensin-(1-7) + PI3K inhibitor, paced + angiotensin-(1-7) + nitric oxide (NO) inhibitor, and paced + angiotensin-(1-7) + A-71915 (ANP receptor antagonist). Rapid atrial pacing was maintained at 600 bpm for 2 h for all groups, except the sham group, and angiotensin-(1-7) (6 μg kg(-1) h(-1)), Mas inhibitor (5.83 μg kg(-1) h(-1)), Akt inhibitor (2.14 μg kg(-1) h(-1)), PI3K inhibitor (2.86 μg kg(-1) h(-1)), NO synthase inhibitor (180 μg kg(-1)h(-1)), or A-71915 (0.30 μg kg(-1) h(-1)) were administered intravenously. Atrial effective refractory periods, inducibility, and duration of atrial fibrillation (pacing cycle lengths: 300, 250, and 200 ms), and left atrial ANP concentrations were measured.
  
  
  RESULTS
  After pacing, the atrial effective refractory periods at the six sites shortened with increased inducibility and duration of atrial fibrillation, which was attenuated by angiotensin-(1-7), and increased ANP concentrations, which was promoted by angiotensin-(1-7) (paced control vs. sham; P < 0.05). All inhibitors and A-71915 blocked the electrophysiological effects of angiotensin-(1-7). ANP secretion induced by angiotensin-(1-7) was also blocked by all inhibitors.
  
  
  CONCLUSIONS
  Angiotensin-(1-7) prevented acute electrical remodeling in canines with acute atrial tachycardia via the angiotensin-(1-7)/Mas/PI3K/Akt/NO signaling pathway. ANP was related to the anti-arrhythmic effects of angiotensin-(1-7).
authors.affiliation: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, People's Republic of China liu_ezh@126.com.
authors.forename: Enzhao
authors.initials: E
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, People's Republic of China.
authors.forename: Guangping
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, People's Republic of China.
authors.forename: Lingshan
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, People's Republic of China.
authors.forename: Wansong
authors.initials: W
authors.lastname: Yang
mesh_terms: D000208:Acute Disease; D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013610:Tachycardia / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000803:Angiotensin I; D009320:Atrial Natriuretic Factor; D009569:Nitric Oxide; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D043562:Receptors, G-Protein-Coupled; C118790:angiotensin I (1-7)
keywords: Atrial fibrillation; angiotensin-(1-7); rapid atrial pacing