Exercise training reduces severity of atherosclerosis in apolipoprotein E knockout mice via nitric oxide.

BACKGROUND: Exercise training may protect against the development of atherosclerosis, although the precise mechanisms are still unknown. The present study assessed the hypothesis that exercise training would reduce the severity of experimental atherosclerosis in apolipoprotein-E (apoE)-deficient mice via nitric oxide (NO).

METHODS AND RESULTS: ApoE-deficient mice fed a high-fat diet underwent exercise training (30 min swimming) 3 times per week for 8 weeks. The exercise group were also given oral N(G)-nitro-L-arginine methylester (L-NAME; 25 mg x kg (-1) x day(-1)), an inhibitor of NO synthase. Fatty streak plaque lesions developed in ApoE-deficient mice fed the high-fat diet, and were suppressed in the mice that underwent swimming training. In contrast, atherosclerotic lesions were not ameliorated in mice that had exercise training plus oral L-NAME treatment. Immunohistochemical analysis revealed that the expression of endothelial NO increased in mice undergoing exercise compared with the mice that did not exercise, and that the expression was suppressed in the mice having exercise plus oral L-NAME treatment. Differences in lesion area did not correlate with any significant alterations in serum lipid levels.

CONCLUSION: Exercise training suppressed atherosclerosis via the NO system.