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Laboratory Research
Valsartan prevents the development of rabbit’s heart failure by restoring calcium uptake ofsarcoplasmic reticulum
Cao Zou, Zhi-Hua Liu, Fu-Zheng Qu, Bin Jiang, Jian-Ping Song,Jie Hui, Xu-Jie Cheng, Lian-Hua Han, Wen-Ping Jiang.J Geriatr Cardiol 2009,6(3):173~177
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Authors:Cao Zou, Zhi-Hua Liu, Fu-Zheng Qu, Bin Jiang, Jian-Ping Song,Jie Hui, Xu-Jie Cheng, Lian-Hua Han, Wen-Ping Jiang1;

Author Affiliation:1.Department of Cardiology, The First Affiliated Hospital of Soochow University Suzhou 215006, China


Abstract: 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, Ser16-phosphorylated phospholamban (p-PLB), PKA and PP1á 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 of PP1αin 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.


calcium, heart failure, sarcoplasmic reticulum, Valsartan
          Published Online:September 28, 2009
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