L-Arginine-NO pathway inhibits the hypertrophic response of cultured cardiomyocytes induced by angiotensin Ⅱ
- VernacularTitle:L-精氨酸-NO途径抑制血管紧张素Ⅱ诱导的心肌细胞肥大反应
- Author:
Tao YANG
;
Wei ZHANG
;
Lei ZHANG
- Publication Type:Journal Article
- Keywords:
L-arginine;
nitric oxide;
angiotensin receptor;
MAPK;
cardiac hypertrophy
- From:
Chinese Pharmacological Bulletin
2003;0(10):-
- CountryChina
- Language:Chinese
-
Abstract:
Aim This study is designed to analyze the influence of L-arginine (L-Arg) on expression level of angiotensin Ⅱ receptors (ATR) and the mitogen-activated protein kinase (MAPK) in cultured cardiomyocytes, with the intention to clarify the mechanisms relative to L-Arg's inhibitory effects on formation of cardiac hypertrophy. Methods Five groups of cardiomyocytes were established: control group, Angiotensin Ⅱ (ATⅡ) group, ATⅡ + Saralasin group, ATⅡ + L-Arg group, ATⅡ + L-Arg+L-NAME (N-nitro-L-arginine methyl ester) group. After 48 hours in supplemented culture, synthetic velocity of protein, NO production, expression level of ATR and p38 MAPK in cardiomyocytes were detected through the [3H]-leucine incorporation method, colorimetry, RT-PCR and western blotting, respectively. Results L-Arg could decrease the expression level of ATR1 and phosphorylated p38 MAPK, enhance NO production and reduce the synthetic velocity of protein in cultured cardiomyocytes stimulated by ATⅡ. Both ATⅡ and L-Arg had no influence on the expression level of angiotensin receptor type 2(ATR 2). Correlation analysis revealed that the relationship of negative correlation was significant between NO production and each of following factors: ATR1 expression level and phosphorylated p38MAPK expression level; As indicated by multiple stepwise regression analysis, not ATR2 expression level, but ATR1 expression level acted as the regression predictor of expression level of phosphorylated p38MAPK. Conclusion By enhancing myocardial NO production, L-Arg-NO pathway inhibits the p38MAPK activation mediated by ATR1, leading to inhibition of the hypertrophic response of cardiomyocytes. ATR2 seems to be independent from the activation process of p38 MAPK.
