NOS inhibition accelerates atherogenesis: reversal by exercise

• Published in: American journal of physiology. Heart and circulatory physiology 2003-08, Vol.54 (2), p.H535-H540
• Main Authors: NIEBAUER, Josef, MAXWELL, Andrew J, LIN, Patrick S, WANG, David, TSAO, Philip S, COOKE, John P
• Format: Article
• Language: English
• Subjects: Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Exercise; Medical sciences; Nitric oxide; Rodents
• ISSN: 0363-6135; 1522-1539

In this study, we assessed the effects of chronic exercise training (12 wk) on atherosclerotic lesion formation in hypercholesterolemic apolipoprotein E-deficient mice (n = 31). At the age of 9 wk, mice were assigned to the following groups: sedentary (Sed; n = 9); exercise (Ex; n = 12); sedentary and oral NG-nitro-L-arginine (L-NNA, Sed-NA; n = 4), or exercise and oral L-NNA (Ex-NA; n = 6). Chronic exercise training was performed on a treadmill for 12 wk (6 times/wk and twice for 1 h/day) at a final speed of 22 m/min, and an 8 degree grade. L-NNA was discontinued 5 days before final treadmill testing. The farthest distance run to exhaustion was observed in Ex-NA mice (Sed: 306 plus or minus 32 m; Ex: 640 plus or minus 87; Sed-NA: 451 plus or minus 109 m; Ex-NA: 820 plus or minus 49 m; all P < 0.05). Lesion formation was assessed in the proximal ascending aorta by dissection microscopy after oil red O staining. The aortas of Sed-NA mice manifested a threefold increase in lesion formation compared with the other groups. This L-NNA-induced lesion formation was reduced by chronic exercise training (Sed, 786 plus or minus 144; Ex, 780 plus or minus 206; Sed-NA, 2,147 plus or minus 522; Ex-NA, 851 plus or minus 253; Sed-NA vs. all other groups: P < 0.001). In conclusion, treatment with oral L-NNA (an nitric oxide synthase antagonist) leads to accelerated atherogenesis in genetically determined hypercholesterolemic mice. This adverse effect can be overcome by chronic exercise training. [PUBLICATION ABSTRACT]