title: Evidence against oxidative stress as mechanism of endothelial dysfunction in methionine loading model.
abstract: Endothelial dysfunction reflects reduced nitric oxide (NO) bioavailability due to either reduced production, inactivation of NO, or reduced smooth muscle responsiveness. Oral methionine loading causes acute endothelial dysfunction in healthy subjects and provides a model in which to study mechanisms. Endothelial function was assessed using flow-mediated dilatation (FMD) of the brachial artery in humans. Three markers of oxidative stress were measured ex vivo in venous blood. NO responsiveness was assessed in vascular smooth muscle and platelets. Oral methionine loading induced endothelial dysfunction (FMD decreased from 2.8 +/- 0.8 to 0.3 +/- 0.3% with methionine and from 2.8 +/- 0.8 to 1.3 +/- 0.3% with placebo; P < 0.05). No significant changes in measures of plasma oxidative stress or in vascular or platelet sensitivity to submaximal doses of NO donors were detected. These data suggest that oxidative stress is not the mechanism of endothelial dysfunction after oral methionine loading. Furthermore, the preservation of vascular and platelet NO sensitivity makes a signal transduction abnormality unlikely.
authors.affiliation: Department of Cardiology, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff CF14 4XN, United Kingdom. nightingaleak@cardiff.ac.uk
authors.forename: A K
authors.initials: AK
authors.lastname: Nightingale
authors.forename: P P
authors.initials: PP
authors.lastname: James
authors.forename: J
authors.initials: J
authors.lastname: Morris-Thurgood
authors.forename: F
authors.initials: F
authors.lastname: Harrold
authors.forename: R
authors.initials: R
authors.lastname: Tong
authors.forename: S K
authors.initials: SK
authors.lastname: Jackson
authors.forename: J R
authors.initials: JR
authors.lastname: Cockcroft
authors.forename: M P
authors.initials: MP
authors.lastname: Frenneaux
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001916:Brachial Artery / Q000378:metabolism; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology*; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008715:Methionine; D008875:Middle Aged; D009566:Nitrates / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D011446:Prospective Studies; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D009566:Nitrates; D017392:Thiobarbituric Acid Reactive Substances; D006710:Homocysteine; D008715:Methionine