OBJECTIVETo 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.

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 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.

RESULTSCompared 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.

CONCLUSIONValsartan improved cardiac function in heart failure rabbits probably via downregulating myocardial CaMK II expression and activity.