Objective: To investigate the effects of simvastatin (SIM)on cardiac hypertrophy and association with calcium channel modulation in rats with myocardial hypertrophy.
Methods: Myocardial hypertrophy was induced by abdominal aortic constriction (AAC) in adult SD rats. Following groups were studied (n=8 each): sham group, AAC group, AAC+ verapamil group (10 mg x kg(-1) x d(-1) per gavage for 4 weeks), AAC +SIM group (10 mg x kg(-1) x d(-1) per gavage for 4 weeks) AAC + SIM + mevalonic acid (50 mg x kg(-1) x d(-1) per gavage for 4 weeks) group. Systolic blood pressure (SBP), echocardiography, heart weight/body weight (HW/BW) and left ventricle weight/body weight (LVW/BW) ratios were measured. The protein and mRNA expressions of L-type calcium channel subunit alpha1 C and T-type calcium channel subunit alpha1 G and alpha1 H were detected by Western blot and RT-PCR respectively.
Results: SBP, HW/BW, LVW/BW, IVS and LVPW thickness, left ventricular weights were significantly increased in AAC rats and these effects could be significantly reduced by verapamil and SIM. The protein and mRNA expressions of alpha1 G and alpha1 H were significantly increased in AAC rats which could also be significantly inhibited by SIM or verapamil. The effects of SIM could be blocked by cotreatment with mevalonic acid. Protein and mRNA expressions of L-type calcium channel alpha1 C were similar among groups.
Conclusion: Similar as verapamil, SIM could prevent AAC induced cardiac hypertrophy, possibly via inhibiting T-type calcium channel subunit alpha1 G and alpha1 H re-expression.