Nitric oxide prevents atorvastatin-induced skeletal muscle dysfunction and alterations in mice

Introduction: Myopathy is the most common side effect of statins. Since nitric oxide (NO) has a key role in regulating skeletal muscle function, we studied whether the NO-donating atorvastatin NCX 6560 could show a better profile on skeletal muscle function and structure compared to atorvastatin. Methods: C57BL/6 mice received atorvastatin 40 mg/kg/day or an equivalent dose of NCX 6560 for 2 months. Muscle function was assessed treadmill test, serum creatine kinase (CK) activity, citrate synthase (CS) activity, and muscle histology. Results: Atorvastatin significantly (P<0.001) reduced muscle endurance, increased serum CK 6-fold, and induced muscle fiber atrophy. Conversely, NCX 6560 preserved muscle function, prevented CK increase and did not modify muscle structure. Interestingly, atorvastatin reduced CS activity, a marker for mitochondrial function, in gastrocnemius, diaphragm and heart, whereas NCX 6560 prevented such decrease. Conclusion: These findings suggest that NO may prevent statin-induced myopathy.