Evidence against oxidative stress as mechanism of endothelial dysfunction in methionine loading model

Endothelial dysfunction reflects reduced nitric oxide (NO) bioavailability due to either reduced production, inactivation of NO, or reduced smooth mus cle responsiveness. Oral methionine loading causes acute endothelial dysfun ction 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 meas ured ex vivo in venous blood. NO responsiveness was assessed in vascular sm ooth muscle and platelets. Oral methionine loading induced endothelial dysf unction (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 ch anges in measures of plasma oxidative stress or in vascular or platelet sen sitivity to submaximal doses of NO donors were detected. These data suggest that oxidative stress is not the mechanism of endothelial dysfunction afte r oral methionine loading. Furthermore, the preservation of vascular and pl atelet NO sensitivity makes a signal transduction abnormality unlikely.