Stimulation of adenosine A1 receptor attenuates angiotensin Ⅱ induced myocardial hypertrophy in neonatal rats via the extracellular signal-regulated kinase signal pathways
10.3760/cma.j.issn.0253-3758.2013.08.015
- VernacularTitle:腺苷A1受体可通过细胞外信号调节激酶通路抑制血管紧张素Ⅱ诱导的心肌细胞肥大
- Author:
Zhi-Ye LI
1
;
Yu-Hong YANG
;
Ling XING
Author Information
1. 450001,郑州大学第二附属医院药学教研室
- Keywords:
Cardiomyopathy,hypertrophic;
Adenosine;
Angiotensin Ⅱ;
Extracellular signal regulated MAP kinases
- From:
Chinese Journal of Cardiology
2013;41(8):698-703
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the impact of adenosine A1 receptor stimulation on extracellular signal-regulated kinase1/2 (ERK1/2) signal pathways on angiotensin Ⅱ (Ang Ⅱ) stimulated cardiomyocytes of neonatal rats in vitro.Methods Cardiomyocytes of neonatal rats were cultured in vitro.Cardiomyocytes hypertrophy was induced by Ang Ⅱ (0.1 μmol/L).The antihypertrophic effect of adenosine A1 receptor stimulation via adenosine A1 receptor agonist R-PIA (1 μ mol/L) was observed in the presence or absence of ERK1/2 inhibitor 1,4-Diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene (U0126) 1 μmol/L,PKC inhibitor Ro-31-8220 (50 nmol/L),and pertussistoxin (PTX,5 mg/L).The total protein content was assayed by the method of Lowry.The expression of mRNA of atrial natriuretic peptide (ANP)was determined by RT-PCR.[Ca2 +] i was measured by confocal microscope using Fluo-3/AM as flouresecent indicator.The relative expression of ERK1/2 was determined by Western blot.Results Compared with normal controlgroup,AngⅡ induced significant cardiomyocyte hypertrophy.Compared with AngⅡ group,R-PIA significantly inhibited Ang Ⅱ-induced increase of the protein content,cardiomyocytes volume and expression of ERK1/2,calciumion fluorescence intensity,similar as U0126 and Ro-31-8220.The inhibitory effects on Ang Ⅱ induced cardiomyocytes hypertrophy of R-PIA were lost when preincubated with PTX.Conclusion Adenosine A1 receptor can inhibit AngⅡ induced cardiomyocyte hypertrophy through downregulating ERK signal pathways and reducing intracellular Ca2+.
