Effects of methionine-induced hyperhomocysteinemia on endothelium-dependent vasodilation and oxidative status in healthy adults

Background-Homocysteine-mediated endothelial dysfunction has been proposed to occur via oxidative stress mechanisms in humans. However, there is contr oversy regarding the effects of homocysteine on endothelia! function and ox idative status, which may in part result from age discrepancy across the st udies. The present study was designed to investigate the aging effect on th e relationship between endothelium-dependent vasodilation and oxidative sta tus in methionine-induced hyperhomocysteinemia. Methods and Results-Plasma homocysteine, phosphatidylcholine hydroperoxide (PCOOH), P-selectin levels, and brachial artery flow-mediated vasodilation were measured at baseline and 4 hours after an oral methionine load (0.1 g/ kg) in 15 younger (21 to 40 years) and 15 older (55 to 70 years) healthy ad ults. Homocysteine increased from 7.3+/-1.3 mu mol/L at baseline to 22.7+/- 5.2 mu mol/L at 4 hours in younger (P<0.001) and from 7.4+/-1.4 to 24.3+/-4 .5 mu mol/L in older adults (P<0.001). PCOOH levels were not significantly different between baseline and 4 hours in both groups (P=0.10 in young; P=0 .14 in old). P-selectin, which is expected to increase during oxidative str ess, was not changed in older (P=0.08) but decreased in younger adults (P=0 .037) at 4 hours, Flow-mediated vasodilation was preserved from 13.1+2.1% a t baseline to 13.5+/-2.8% at 4 hours in younger (P=0.49) and decreased from 12.8+/-2.4% to 8.5+/-2.8% in older adults (P<0.001). Conclusions-The present study demonstrates that endothelial dysfunction cau sed by methionine-induced hyperhomocysteinemia is age-related and is mediat ed through impaired nitric oxide activity without change of oxidative statu s. Our data do not support previous hypotheses that endothelial damage by h omocysteine is via oxidative stress mechanism in humans. (Circulation, 2000 ;101:485-490.).