OBJECTIVETo investigate the effects of simvastatin on the left ventricular (LV) expression of transient outward potassium channel in rabbits with experimental heart failure (HF).

METHODSHF model was established by ligating the left anterior descending coronary artery of rabbits. Rabbits were randomized into simvastatin group (HF + S, 10 mg x kg(-1) x d(-1) for 10 weeks, n = 8), HF group (n = 9), and sham group (n = 9). Left ventricular remodeling and function were evaluated by echocardiography and hemodynamic measurements 10 weeks after operation. The mRNA and protein expressions of K(v)1.4, K(v)4.2 and K(v)4.3 potassium channel alpha subunit in LV were determined by semi-quantitative RT-PCR and Western blot.

RESULTSSimvastatin attenuated LV remodeling and improved cardiac function. The mRNA and protein expressions of K(v)1.4, K(v)4.2 and K(v)4.3 potassium channel alpha subunit in HF rabbits (0.48 +/- 0.09, 0.37 +/- 0.07, 0.42 +/- 0.11; 0.33 +/- 0.09, 0.22 +/- 0.07, 0.29 +/- 0.11) were significantly decreased compared with sham rabbits (0.85 +/- 0.08, 0.66 +/- 0.07, 0.67 +/- 0.08; 0.68 +/- 0.13, 0.53 +/- 0.15, 0.49 +/- 0.10, all P < 0.01), and these decreases could be attenuated by simvastatin (0.77 +/- 0.10, 0.50 +/- 0.10, 0.57 +/- 0.12; 0.58 +/- 0.10, 0.36 +/- 0.10, 0.43 +/- 0.12, all P < 0.01 vs. HF).

CONCLUSIONSimvastatin not only attenuated LV remodeling and improved LV function but also prevented the downregulation of LV transient outward potassium channel expressions in rabbits with experimental HF.