Atorvastatin protects endothelium by decreasing asymmetric dimethylarginine in dyslipidemia rats

BACKGROUND: Asymmetric Dimethylarginine (ADMA) is an inhibitor of endogenous nitric oxide synthase, which is the key synthase for nitric oxide (NO) production. Whether statins could protect endothelium by reducing ADMA concentration is unclear, and whether this effect is associated with the dose of statins usage is also needed further studied. METHODS: Dyslipidemia rat model was produced by giving high-fat and high-cholesterol diet for 8 weeks. Thereafter, low-dose (5 mg/kg body weight/day) and high-dose (20 mg/kg body weight/day) atorvastatin were orally prescribed for 4 weeks. Parameters of interest including lipid profiles, inflammatory and oxidative markers, NO production and plasma levels of ADMA and ADMA concentration of myocardium were evaluated. Liver enzymes and creatinine kinase (CK) were also detected for safety concern. RESULTS: At baseline, all parameters were comparable between the sham and the dyslipidemia groups. At 8 weeks of dyslipidemia establishment, as compared to the sham group, body weight and lipid profiles were significantly elevated, and plasma levels of C-reactive protein (CRP), malondialdehyde (MDA) and ADMA were concomitantly increased in accompanying with NO reduction in the dyslipidemia groups. With 4 weeks of atorvastatin therapy, as compared to the control group, lipid disorders and NO production were improved, and plasma levels of CRP, MDA and ADMA were significantly decreased in the high-dose atorvastatin group. ADMA concentration of cardiac tissues was also significantly reduced in the high-dose atorvastatin group. Notably, there was a trend to similar effects which did not reach statistical significance in the low-dose atorvastatin group when compared to the control group. Liver enzyme and CK were comparable after 4 weeks of atorvastatin therapy between groups. CONCLUSION: In rats with dyslipidemia, atorvastatin therapy could reduce plasma level of ADMA and ADMA concentration in cardiac tissues, and these effects are associated with the dose of atorvastatin therapy.