Effects of long-term administration of methionine on vascular endothelium in rabbits

Background and Aim: We studied the effects of long-term methionine administration on the vascular endothelium of Japanese white rabbits. Methods and Results: Eleven rabbits were divided into a control group (n=6) and a methionine-fed group (n=5), and reared for 22 weeks. Blood samples were collected at baseline and after 22 weeks for the measurement of serum homocysteine and cysteine, serum lipids and serum superoxide dismutase activity. At the end of experiments, the animals were sacrificed, and the thoracic aorta was removed for the measurement of isometric tension and histopathological examination. The blood samples taken from the methionine group in the 22(nd) week showed slight but significant increases in serum homocysteine and cysteine levels (Hcy: 13.7 +/- 1.4 vs 21.0 +/- 4.9, p<0.01; Cys: 241.6 +/- 37.8 vs 342.6 +/- 35.0, p<0.01). In the isometric tension experiments, the methionine group had a significantly decreased (p<0.01) vasodilatation reaction induced by acetylcholine, an endothelium-dependent vasodilator. The histopathological examination (immunostaining in response to eNOS and tissue factor) showed significant increases in endothelium expression in the methionine group before atherosclerotic changes appeared. Conclusions: The above results suggest that vascular endothelial dysfunction played an important role in the atherosclerosis occurring after excess methionine feeding.