Effects of simvastatin and L-arginine on vasodilation,nitric oxide metabolites and endogenous NOS inhibitors in hypercholesterolemic subjects |
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Authors: | Pereira Edimar C Bertolami Marcelo C Faludi André A Salem Mohamed Bersch Daniela Abdalla Dulcineia S P |
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Affiliation: | Faculdade de Ciências Farmacêuticas, Universidade de S?o Paulo, Av. Prof. Lineu Prates, 580, Cidade Universitária-Butant?, 05508-900 S?o Paulo, Brazil. |
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Abstract: | 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. |
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Keywords: | Simvastatin l -arginine Endothelial Function Endogenous Nos Inhibitors Nitric Oxide Hypercholesterolemia |
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