L-arginine Protects Cardiac and Smooth Muscle Against Statin-Induced Myopathy

Abstract

High dose statin therapy has been shown to negatively influence muscle function with reactive oxygen species, inflammation and nitric oxide levels as contributing mechanisms. Typically, skeletal muscle shows the most damage, however other muscle types may also be affected. This study aimed to assess the efficacy of L-arginine (L-arg) to protect cardiac and smooth muscle in an animal model of statin-induced myopathy (SIM). 10-12 week-old female Wistar (WIS) rats were randomly assigned to one of four treatment groups; control (CON), SIM (80 mg/kg/day of simvastatin), control + L-arg (L-arg; 100 mg/kg/day) and SIM + L-arg (SIM + L-arg). Treatment persisted for two weeks after which assessments of cardiac and smooth muscle function were made. The onset of SIM was associated with significant increases in left ventricular mass (WIS 2.45 m/gbwt; SIM 2.79 mg/gbwt), hydroxyproline content, alterations in nitric oxide levels and prolongation of cardiac action potential duration. The administration of L-arginine to SIM animals was noted to reduce left ventricular mass, hydroxyproline (SIM 6.65 mg/ml; SIM + L-arg 2.21 mg/ml) levels, restore nitric oxide concentration and prevent prolongation of action potentials. Notably the administration of high dose statin therapy improved endothelial dependent and independent vessel function which was further improved via L-arg co-therapy. These findings suggest high dose statin therapy enhanced vessel function but negatively impacted on left ventricular structure and function. Cardiac remodelling and sustained blood vessel function from SIM can be improved with L-arg co-therapy in young female rats.