Effects of simvastatin and L-arginine on vasodilation, nitric oxide metabolites and endogenous NOS inhibitors in hypercholesterolemic subjects

Hypercholesterolemia is linked to endothelial dysfunction and enhancement of the endogenous inhibitor of NO synthase. The statins have lipid-lowering and pleiotropic properties, which could exert protective effects on the endothelium in hypercholesterolemia. The association of L-arginine with simvastatin could promote a further improvement on endothelial function in this condition. Thus, we investigated whether simvastatin, with or without supplementation with L-arginine, could improve endothelium-dependent vasodilation. In this study, 25 hypercholesterolemic subjects were treated according to the following protocol: washout period of 1 month; simvastatin (20 mg/day) for 2 months; simvastatin (20 mg/day) + L-arginine (7 g/day) for 2 months. From these patients, 10 were chosen at random for evaluation of vascular function by high resolution ultrassonography of the brachial artery. In subjects treated with simvastatin plus L-arginine, an increase of L-arginine levels (68%) and L-arginine/asymmetric dimethylarginine (ADMA) ratio (67%) were observed. Simvastatin reduced the plasma concentrations of NO metabolites nitrite + nitrate (NOx: 34%), S-nitrosothiols (RSNO:42%), total cholesterol (25%), low density lipoprotein (LDL)-cholesterol (36%) and the LDL-cholesterol/high density lipoprotein (HDL)-cholesterol ratio (34%). Simvastatin, associated or not to L-arginine, did not affect ADMA levels and endothelium-dependent vasodilation. Our data showed that simvastatin reduced the plasma concentrations of NOx and RSNO without affecting either the levels of ADMA or endothelium-dependent vasodilation in hypercholesterolemia.