NG-nitro-L-arginine methyl ester(L-NAME)の投与は運動による動脈硬化抑制効果を阻害する

The Supplementation of NG-Nitro-L-Arginine Methyl Ester(L-NAME) Inhibits Suppressive Effects of Exercise in Experimental Atherosclerosis

要旨　目的：適度な有酸素運動が動脈硬化を抑制すること，またnitric oxide(NO)産生の抑制が動脈硬化の進展を促進することはすでに報告されている．今回われわれは，アポリポプロテインE(アポE)ノックアウトマウスに対して，N^G-nitro-L-arginine methyl ester(L-NAME)の補充と運動を単独または同時に行い，運動とNOの効果について検討した．

　方法：動脈硬化はアポEノックアウトマウスに高脂肪食を与え作成した．飲水中のL-NAME(0.1mg/ml)は自由に飲水させ，運動は水泳を1回につき30分，週3回，8週間にわたって行った．大動脈のoil red O染色を比較することで動脈硬化の病変の評価を行った．

　結果：運動群は非運動群より動脈硬化の病変が減少した．運動群と比べ，運動＋L-NAME補充群で病変が有意に増加したが，非運動群とL-NAME補充群では差はみられなかった．endothelial nitric oxide synthase(eNOS)の発現はL-NAMEの投与で減少した．

　結論：運動による動脈硬化進展抑制効果がL-NAMEの補充により失われたことから，その抑制効果には運動により発現増加するNOの役割が重要であるのではないかと考えられた．

　［Objectives］ It has already been reported that moderate aerobic exercise suppresses experimental atherosclerosis and that decreased production of nitric oxide(NO) accelerates experimental atherosclerosis. In this study, we investigated the effect of NO in exercise-trained apolipoprotein E-deficient mice by supplementation of N^G-nitro-L-arginine methyl ester(L-NAME).

　［Methods］ Atherosclerosis was induced in the mice fed on a high-fat diet. The mice were given free access to L-NAME(0.1mg/ml) in drinking water. Exercise was performed for 30 minutes 3 times per week on alternate days over 8 weeks. Oil red-O staining was carried out in the aorta for all groups, and the atherosclerotic lesions were assessed and compared among the groups.

　［Results］ In the control groups, the atherosclerotic lesion in the exercise-group was less severe than in the non-exercise group. In exercise groups, the lesion of the L-NAME-supplemented group significantly increased compared with the control group. However, the difference was not significant among the non-exercice groups. Endothelial nitric oxide synthase(eNOS) expression of the L-NAME-supplemented groups was reduced compared with the control groups.

　［Conclusions］ Suppressive effects against atherosclerosis by exercise were restored by the supplementation of L-NAME. Accordingly, it was confirmed that suppression of atherosclerosis by exercise was mediated via NO.