title: An adenosine A1 agonist 2-chloro-N6 cyclopentyladenosine inhibits the angiotensin II-induced cardiomyocyte hypertrophy through the calcineurin pathway.
abstract: OBJECTIVE
  The aim of this investigation was to study the underlying mechanism of an adenosine A1 receptor agonist 2-chloro-N6 cyclopentyladenosine (CCPA) inhibiting cardiomyocyte hypertrophy induced by angiotensin II (AngII).
  
  
  METHODS
  Neonatal rat cardiomyocytes were treated with AngII to generate a cardiomyocyte hypertrophy model. Cardiomyocyte cultures were randomized into 5 groups: control; AngII; AngII + cyclosporin A (CsA); AngII + CCPA, and AngII + CCPA + DPCPX. Cardiomyocyte viability was measured by MTT assay. Protein synthesis was assessed by the application of (3)H leucine ((3)H-Leu) incorporation into protein. The mRNA expressions of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), β-myosin heavy chain (β-MHC) and calcineurin Aβ (CnAβ) were measured by real-time quantitative PCR. The protein level of CnAβ was dissected by Western blotting.
  
  
  RESULTS
  AngII administration at lower concentrations increased the cardiomyocytes viabilities gradually. Surface area, mRNA expressions of ANP, BNP and β-MHC, and (3)H-Leu incorporation of AngII-induced cardiomyocytes were increased in a dose-dependent manner. As a calcineurin-specific inhibitor, CsA inhibited (3)H-Leu incorporation, surface area, mRNA expressions of ANP, BNP, β-MHC, CnAβ and protein expression of CnAβ of AngII-induced cardiomyocytes. CCPA also suppressed the mRNA and protein expressions of CnAβ and exerted antihypertrophic effects to a greater degree than CsA. The inhibition of CCPA on cardiomyocyte hypertrophy was counteracted by the A1 receptor antagonist DPCPX.
  
  
  CONCLUSIONS
  The A1 receptor agonist CCPA could significantly inhibit AngII-induced cardiomyocyte hypertrophy via the calcineurin signaling pathway.
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China.
authors.forename: Xingliang
authors.initials: X
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Xia
authors.forename: Dandan
authors.initials: D
authors.lastname: Qian
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Lin
authors.forename: Xiulan
authors.initials: X
authors.lastname: Huang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Tan
mesh_terms: D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: D058907:Adenosine A1 Receptor Agonists; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D016572:Cyclosporine; D019703:Calcineurin; D018995:Myosin Heavy Chains