title: Effects of simvastatin and L-arginine on vasodilation, nitric oxide metabolites and endogenous NOS inhibitors in hypercholesterolemic subjects.
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 ultrasonography 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.
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Prof. Lineu Prates, 580, Cidade Universitária-Butantã, 05508-900 São Paulo, Brazil.
authors.forename: Edimar C
authors.initials: EC
authors.lastname: Pereira
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Bertolami
authors.forename: André A
authors.initials: AA
authors.lastname: Faludi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Salem
authors.forename: Daniela
authors.initials: D
authors.lastname: Bersch
authors.forename: Dulcineia S P
authors.initials: DS
authors.lastname: Abdalla
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D005609:Free Radicals / Q000097:blood; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000097:blood; D009573:Nitrites / Q000097:blood; D026403:S-Nitrosothiols / Q000097:blood; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000924:Anticholesteremic Agents; D005609:Free Radicals; D008055:Lipids; D009566:Nitrates; D009573:Nitrites; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019821:Simvastatin; D019001:Nitric Oxide Synthase