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Valsartan prevents the development of rabbit＇s heart failure by restoring calcium uptake of sarcoplasmic reticulum

Journal of Geriatric Cardiology 2009年第3期6卷 173-177页

作者： Cao Zou Zhi-Hua Liu Fu-Zheng Qu Bin Jiang Jian-Ping Song Jie Hui Xu-Jie Cheng Lian-Hua Han Wen-Ping Jiang Department of Cardiology The First Affiliated Hospital of Soochow University Suzhou 215006China

Objective Clinical evidence has suggested that AT1 receptor blocker （ARB） could prevent the development of heart failure. Decreased sarcoplasmic reticulum（SR） Ca2＋ content, which is due to reduced SR calcium reuptake by SERCA2a, is responsible for defective systolic function in failing heart. To better understand how ARB could improve cardiac systolic dysfunction, we studied the effects of Valsartan on calcium reuptake of SR and its regulatory proteins in heart failure rabbits. Methods Thirty rabbits were divided into three groups： sham rabbits（controls, n=11）, rabbits with heart failure treated with Valsartan （n=11） and rabbits with heart failure but without Valsartan treatment （n=8）.Rabbit heart failure model was established by volume plus pressure overload. Cardiac function was measured by echocardiography, SR calcium uptake was determined by measuring extra vesicular free [Ca2＋] changes in a fluorescence spectrophotometer. SERCA2a, Ser 16-phosphorylated phospholamban （p-PLB）, PKA and PP 1 a protein abundance were determined by use of Western blot analysis. Results Compared to control rabbits, the ejection fractions in the HF rabbits were significantly decreased （P〈0.05）, these changes could be significantly attenuated by Valsartan treatment （P〈0.05）.Calcium reuptake of SR, activity of SERCA2a and PKA decreased in heart failing myocytes （P〈0.05）, with down regulations of p-PLB, SERCA2a and PKA, but up regulation ofPP la in ventricular samples from the failing rabbits （P〈0.05）. All of these changes were attenuated by Valsartan treatment （all P〈0.05）. Conclusion Valsartan improved cardiac function in volume plus pressure overload induced heart failure of rabbits possibly by restoring the SR calcium uptake resulted from attenuating the activities and expressions of SERCA2a and its regulatory proteins （J Geriatr Cardio12009; 6：173-177）.

关键词： calcium heart failure sarcoplasrnic reticulum Valsartan

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