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An Adenosine A1 Agonist 2-chloro-N6 Cyclopentyladenosine Inhibits the Angiotensin II-induced Cardiomyocyte Hypertrophy Through the Calcineurin Pathway

An Adenosine A1 Agonist 2-chloro-N6 Cyclopentyladenosine Inhibits the Angiotensin II-induced Cardiomyocyte Hypertrophy Through the Calcineurin Pathway

Xingliang Zhang, Juan Xia, Dandan Qian, Yang Wang, Yongwen Lin, Xiulan Huang, Jianxin Tan

Cardiology. 2014;129(3):153-62.

PMID: 25277512

Abstract:

Objectives:
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.
Conclusion:
The A1 receptor agonist CCPA could significantly inhibit AngII-induced cardiomyocyte hypertrophy via the calcineurin signaling pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP41552823	N6-Cyclopentyladenosine		41552-82-3	Price

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