[Effects of valsartan on myocardial calcium/calmodulin-dependent protein kinase-II expression and activity in a rabbit model of heart failure].

OBJECTIVE: To investigate the effects of valsartan on myocardial expression and activity of calcium/calmodulin-dependent protein kinase-II (CaMK II) in a rabbit model of heart failure. METHODS: Rabbits 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 mg x kg(-1) x d(-1), n = 9 each). Seven weeks later, echocardiography and hemodynamic examinations were performed and myocardial CaMK II expression and activity were detected by Western blot and CaMK II activity assay kit, respectively. RESULTS: Compared with the sham operated rabbits, left ventricular mass index [LVMI (3.61 +/- 0.09) g/kg vs. (1.32 +/- 0.06) g/kg, P<0.05] and end-diastolic pressure [LVEDP (23.00 +/- 2.37) mm Hg (1 mm Hg = 0.133 kPa) vs. (-1.50 +/- 0.5) mm Hg, P<0.05] were significantly increased while left ventricular shortening fractions [LVFS (17.38 +/- 3.13)% vs. (37.83 +/- 3.58)%, P<0.05] and ejection fraction [LVEF (38.50 +/- 6.07)% vs. (71.92 +/- 4. 56)%, P<0.05] were significantly decreased (all P<0.05) in heart failure rabbits, these changes could be significantly attenuated by valsartan treatment: LVMI [(2.07 +/- 0.14) g/kg vs. (3.61 +/- 0.09) g/kg, P<0.05], LVEDP [(2.17 +/- 0.72) mm Hg vs. (23.00 +/- 2.37) mm Hg, P<0.05], LVFS [(33.83 +/- 2.85)% vs. (17.38 +/- 3.13)%, P<0.05] and LVEF [(64.45 +/- 3.66)% vs. (38.50 +/- 6.07)%, P<0.05]. CaMK II expression (1.45 +/- 0.13 vs 0.89 +/- 0.05, 1.13 +/- 0.12, P<0.05) and activity [(3.54 +/- 0.17) pmol x min(-1) x microg(-1) vs. (2.18 +/- 0.13) pmol x min(-1) x microg(-1), (2.79 +/- 0.14) pmol x min(-1) x microg(-1), P<0.05] in heart failure rabbits were significantly increased than those sham operated rabbits which could be significantly attenuated by valsartan treatment. CONCLUSION: Valsartan improved cardiac function in heart failure rabbits probably via downregulating myocardial CaMK II expression and activity.

[Effects of valsartan on sarcoplasmic reticulum calcium adenosine triphosphatase, protein kinase A and protein phosphatase 1 alpha in a rabbit model of heart failure].

OBJECTIVE: To 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. METHODS: Rabbits 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. RESULTS: Compared 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). CONCLUSION: Valsartan 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.