Effects of valsartan on sarcoplasmic reticulum calcium adenosine triphosphatase, protein kinase A and protein phosphatase 1 alpha in a rabbit model of heart failure.
- Author:
Fu-Zheng QU
1
;
Zhi-Hua LIU
;
Bin JIANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cyclic AMP-Dependent Protein Kinases; metabolism; Female; Heart Failure; drug therapy; metabolism; Male; Protein Phosphatase 1; metabolism; Rabbits; Sarcoplasmic Reticulum; drug effects; metabolism; Sarcoplasmic Reticulum Calcium-Transporting ATPases; metabolism; Tetrazoles; pharmacology; therapeutic use; Valine; analogs & derivatives; pharmacology; therapeutic use; Valsartan
- From: Chinese Journal of Cardiology 2008;36(9):790-793
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of valsartan on expressions of myocardial sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2), protein kinase A (PKA) and protein phosphatase 1 alpha (PP1alpha) in a rabbit model of heart failure.
METHODSRabbits were divided into sham-operated group, heart failure group (volume overload by aortic valve destruction induced aortic insufficiency plus pressure overload induced by abdominal aortic banding) and heart failure plus valsartan (20 mgxkg(-1)xd(-1), n = 6 each). Seven weeks later, echocardiography examination was performed and SERCA2, PKA, PP1alpha protein and mRNA expressions were detected by Western blot and RT-PCR.
RESULTSCompared with the with sham operated rabbits, LVMI and LVEDP in heart failure rabbits were significantly increased while left ventricular shorten fraction (LVFS) and ejection fraction (EF) were significantly decreased (all P < 0.05), these changes could be significantly attenuated by valsartan treatment (all P < 0.05). SERCA2, PKA expressions at protein and mRNA levels were significantly downregulated and PP1alpha expressions significantly upregulated in heart failure rabbits than sham operated rabbits (all P < 0.05) and these changes could be significantly attenuated by valsartan (all P < 0.05).
CONCLUSIONValsartan improved cardiac function in volume and pressure overload induced heart failure rabbits possibly by upregulating expressions of myocardial SERCA2, PKA and downregulating expression of myocardial PP1alpha.
