The Role Of Reactive Oxygen Species In Cardiohypertrophy Which Induced By The Vascular-systolic Substances

Object To find the role of ROS in increased paracrine of hypertrophic cardiomyocytes induced by the vasoconstrictors including ET-1 ,AngⅡ.Methods Neonatal cardiac myocytes were cultured and stimulated by ET-1 and AngⅡ. N-acetylcysteine was used to block the intracellular synthesis of ROS which induced by ET-1,AngⅡetc in experiment. There were five groups which were control group, ET-1 group, AngⅡgroup, ET-1 plus N-acetylcysteine group and AngⅡplus N-acetylcysteine group in the experiment. 2,7-dichlorofluorescin dictate(DCF-DA), a kind of ROS-sensitive probe, was used to examine the intracellular ROS. The expression of preproendothelin-1 gene was examined with RT-PCR assay.Results N-acetylcysteine,a sort of antioxidant,can block the synthesis of ROS and the expression of endothelin-1 gene significantly。Compared with the control group, the fluorescence intensity of intercellular DCF-DA increased by 3.0%, 4.8%, 108.8%, 104.9% in N-acetylcysteine plus AngⅡgroup, N-acetylcysteine plus ET-1 group, ET-1 alone group and AngⅡalone group respectively. Compared with the control group, the expression of Prepro-ET increased by 3.8%, 2.9%, 52.4%, 51.1% in N-acetylcysteine plus ET-1 group, N-acetylcysteine plus AngⅡgroup, ET-1 alone group and AngⅡalone group respectively.Conclusion Compared with the control group, the fluorescence intensity of intercellular DCF-DA increased significantly in ET-1 alone group and AngⅡalone group. But in the N-acetylcysteine plus AngⅡgroup and N-acetylcysteine plus ET-1 group, the fluorescence intensity of intercellular DCF-DA didn't increase significantly. It indicates that ROS is necessary in vasoconstrictor-induced cardiomyocyte hypertrophy. And analogic results took place in the expression of endothelin gene. We can predict that ROS plays a critical Role in the functional deterioration of left ventricles during the transition from compensatory hypertrophy to congestive heart failure.