[Stimulation of adenosine A1 receptor attenuates angiotensin II induced myocardial hypertrophy in neonatal rats via the extracellular signal-regulated kinase signal pathways].
OBJECTIVE
To observe the impact of adenosine A1 receptor stimulation on extracellular signal-regulated kinase 1/2 (ERK1/2) signal pathways on angiotensin II (AngII) stimulated cardiomyocytes of neonatal rats in vitro.


METHODS
Cardiomyocytes of neonatal rats were cultured in vitro. Cardiomyocytes hypertrophy was induced by AngII (0.1 µmol/L). The antihypertrophic effect of adenosine A1 receptor stimulation via adenosine A1 receptor agonist R-PIA (1 µmol/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 pertussis toxin (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. [Ca(2+)]i was measured by confocal microscope using Fluo-3/AM as fluorescent indicator. The relative expression of ERK1/2 was determined by Western blot.


RESULTS
Compared with normal control group, AngII induced significant cardiomyocyte hypertrophy. Compared with AngII group, R-PIA significantly inhibited AngII-induced increase of the protein content, cardiomyocytes volume and expression of ERK1/2, calcium ion fluorescence intensity, similar as U0126 and Ro-31-8220. The inhibitory effects on AngII induced cardiomyocytes hypertrophy of R-PIA were lost when preincubated with PTX.


CONCLUSIONS
Adenosine A1 receptor can inhibit AngII induced cardiomyocyte hypertrophy through downregulating ERK signal pathways and reducing intracellular Ca(2+).
Pharmacy Department, Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China.
Zhi-Ye
ZY
Li
Yu-Hong
YH
Yang
Ling
L
Xing
D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced / Q000517:prevention & control; D002478:Cells, Cultured; D005260:Female; D020935:MAP Kinase Signaling System; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism*
D058907:Adenosine A1 Receptor Agonists; D043682:Receptor, Adenosine A1; D000804:Angiotensin II; D002118:Calcium