The Role Of Oxidative Stress In Cardiac Hypertrophy Induced By Pressure Overload

Objective:To establish the rat model of left ventricular hypertrophy in hypertensive rats by Abdominal Aorta Constriction(AAC) and to investigate the role of oxidative stress in cardiac hypertrophy induced by pressure overload and the benefit effect of antioxidants treatment.Methods:1. Establish the rat model of left ventricular hypertrophy: Abdominal aorta constriction or sham operation were performed on 180-200 g male Sprague Dawley rats.2. Groups: These rats were randomly divided into 4 groups:(1) Sham group(2)AAC group(3) Sham group with NAC treatment(4)AAC group with NAC treatment. The last two groups were treated by NAC at the dosage of 500mg/kg/day respectively via intragastric administration for 2 weeks.3.Methods: Before sacrificed, echocardiographic, hemodynamic and cardiac morphological data were collected again for comparison.Results:2 weeks after abdominal aorta constriction, compared with sham group, HR、SBP、DBP 、 MBP 、 LVSP of AAC group rats increased significantly(P < 0.01), and a remarkable increase of LVEDP(P < 0.05). Besides, HW/BW and LVW/BW of AAC group also increased significantly(P<0.05). Cardiac morphological assessments showed a degree of disarrangement of myocardial cells,which contained a bigger and deformed nucleus and a significant increase of the myocyte cross-sectional area of AAC group versus Sham group(P < 0.05), indicated that there was a significant cardiovascular remodeling in the AAC group compared with the sham group after 2 weeks post-operatively. The IHC results showed over-expression of several proteins in AAC group, including atrial natriuretic peptide(ANP) and phosphorylated extracellular signal-regulated kinase(p-ERK)(P < 0.05). But ±dp/dt was no significant difference between two groups above. After treatment by NAC for 2 weeks, there was a significant decrease of DBP and MBP in AAC+NAC group(P<0.01) compared with AAC group,and the LVEDP, HR, SBP and LVSP of AAC+NAC group showed tendency to decrease,with no significant difference(P > 0.05). There was a significant decrease of the myocyte cross-sectional area of AAC+NAC group(P<0.05) and the expression of ANP and p-ERK down-regulated significantly(P<0.05) versus Sham group.Conclusion:The rat model of left ventricular hypertrophy by Abdominal Aorta Constriction proved to be success. Antioxidant NAC appeared to help ward off high blood pressure in AAC rats, ameliorate cardiac and myocyte hypertrophy, as well as alleviate cardiac remodeling and improve diastolic function, which contained the effect of cardiac protection. May be the heart protection effect of NAC was connected with diminishing the activation of MAPK/ERK pathway.