title: The potential role of atrial natriuretic peptide in the effects of Angiotensin-(1-7) in a chronic atrial tachycardia canine model.
abstract: OBJECTIVE
  The objective of this article is to investigate the possible role of atrial natriuretic peptide (ANP) in Angiotensin-(1-7) (Ang-(1-7)) signaling pathway on atrial electrical and structural remodeling in a chronic rapid atrial pacing canine model.
  
  
  METHODS
  Twenty-four dogs were randomly assigned to four groups: a sham group, paced control group, a paced + Ang-(1-7) group and a paced + Ang-(1-7) + A-71915 group. Atrial rapid pacing (ARP) at 600 bpm was maintained for 14 days except in the animals from the sham group. During the pacing, Ang-(1-7) (6 μg•kg-1•h-1) or Ang-(1-7) (6 μg•kg-1•h-1) + A-71915 (ANP receptor antagonist, 0.30 μg•kg-1•h-1) were given intravenously, respectively. After pacing, it was measured that electrophysiological parameters including atrial effective refractory periods (ERPs), inducibility and duration of atrial fibrillation (AF), ICaL and INa changed, where ICaL refers to voltage-dependent L-type Ca(2+) current and INa refers to cardiac sodium current. Then, the fibrosis and the expression of Cav1.2, INav1.5α subunit, TGF-β1 and ANP in atria were assessed.
  
  
  RESULTS
  After ARP, compared with the sham group, the atrial ERPs at six sites in each dog were shortened with the increasing in inducibility and duration of AF in the paced control group. The density of ICaL, INa and the expression of Cav1.2, INav1.5α subunit mRNA were decreased. Atrial tissue from the paced dogs showed significant interstitial fibrosis. The expression of TGF-β1 and ANP in mRNA and protein levels were increased. Compared with the paced control group, the shortening of atrial ERPs, and the increasing of inducibility and duration of AF induced by ARP were alleviated by Ang-(1-7) treatment (p < 0.05). The density of ICaL and INa and the expression of Cav1.2 and INav1.5α subunit mRNA were slightly decreased. Atrial tissue showed less interstitial fibrosis after Ang-(1-7) treatment. The increasing of ANP expression was improved by Ang-(1-7), while the increasing of TGF-β1 expression was alleviated by Ang-(1-7) (p < 0.05). A-71915 treatment blocked the beneficial effects of Ang-(1-7) on the aforementioned electrophysiological parameters and atrial fibrosis. And A-71915 treatment blocked Ang-(1-7), improving the expression of TGF-β1.
  
  
  CONCLUSIONS
  Ang-(1-7) prevented atrial structural and electrical remodeling induced by ARP. Furthermore, Ang-(1-7) promoted ANP secretion, and ANP played a crucial role in the cardiac protection of the former.
authors.affiliation: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, 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: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, People's Republic of China.
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, 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: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, 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: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, 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: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, 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
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013610:Tachycardia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D021122:Protein Subunits; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D009320:Atrial Natriuretic Factor; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: Ang-(1–7); Atrial fibrillation; atrial natriuretic peptide; rapid atrial pacing