title: Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults.
abstract: In hypercholesterolemic rabbits, oral L-arginine (the substrate for endothelium derived nitric oxide) attenuates endothelial dysfunction and atheroma formation, but the effect in hypercholesterolemic humans is unknown. Using high resolution external ultrasound, we studied arterial physiology in 27 hypercholesterolemic subjects aged 29+/-5 (19-40) years, with known endothelial dysfunction and LDL-cholesterol levels of 238+/-43 mg/dl. Each subject was studied before and after 4 wk of L-arginine (7 grams x 3/day) or placebo powder, with 4 wk washout, in a randomized double-blind crossover study. Brachial artery diameter was measured at rest, during increased flow (causing endothelium-dependent dilation, EDD) and after sublingual glyceryl trinitrate (causing endothelium-independent dilation). After oral L-arginine, plasma L-arginine levels rose from 115+/-103 to 231+/-125 micromol/liter (P<0.001), and EDD improved from 1.7+/-1.3 to 5.6+/-3.0% (P<0.001). In contrast there was no significant change in response to glyceryl trinitrate. After placebo there were no changes in endothelium-dependent or independent vascular responses. Lipid levels were unchanged after L-arginine and placebo. Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process.
authors.affiliation: Cardiothoracic Unit, Great Ormond Street Hospital for Children NHS Trust, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Clarkson
authors.forename: M R
authors.initials: MR
authors.lastname: Adams
authors.forename: A J
authors.initials: AJ
authors.lastname: Powe
authors.forename: A E
authors.initials: AE
authors.lastname: Donald
authors.forename: R
authors.initials: R
authors.lastname: McCredie
authors.forename: J
authors.initials: J
authors.lastname: Robinson
authors.forename: S N
authors.initials: SN
authors.lastname: McCarthy
authors.forename: A
authors.initials: A
authors.lastname: Keech
authors.forename: D S
authors.initials: DS
authors.lastname: Celermajer
authors.forename: J E
authors.initials: JE
authors.lastname: Deanfield
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D001916:Brachial Artery; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017270:Lipoprotein(a) / Q000097:blood; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005996:Nitroglycerin / Q000494:pharmacology; D010919:Placebos; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D010919:Placebos; D014280:Triglycerides; D001120:Arginine; D002784:Cholesterol; D005996:Nitroglycerin