The Regulation of MKP-1 in Cardiomyocyte Hypertrophic Response Induced by Angiotensin II

Objective The study was to examine the MAPK activity and protein expression in the cardiomyocyte hypertrophic response induced by angiotensin Ⅱ(AngⅡ). Method (1) Neonatal rat cardiomyocyte hypertrophic response was assayed by protein synthesis rate. (2) Protein expression of Phosphorlated MAPK and MKP-1 were detected by Western blotting. Result (1) AngⅡ induced promotion of 3H-leucine incorporation in dose-dependent manner. Pretreatment with CV11974, a selective AT 1 receptor antagonist, or PD098059, a specific MEK inhibitor, cardiomyocyte hypertrophic response induced by AngⅡ could be inhibited by 85% and 32 5%, respectively.(2) Pretreatment of cardio myocyte with AngⅡ for 5 min, p44MAPK and p42MAPK protein expression began to increase,the peak effect was at 30 min and last for 2 h; while pretreatment with CV11974(0.1 mmol/L) or PD098059 (50 μmol/L), AngⅡ-induced increase in (p44+ p42)MAPK were inhibited by 89% and 81%, respectively. Conclusion The results suggest that activation of MAPK may play an important role in AngⅡ-induce hypertrophic response in neonatal rat cardiomyocyte, and other signal pathway may also participated in AngⅡ-induced cardiomyocyte hypertrophic response.