NOS inhibition accelerates atherogenesis: Reversal by exercise

Josef Niebauer, Andrew J. Maxwell, Patrick S. Lin, David Wang, Philip S. Tsao, John P. Cooke

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

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° 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 ± 32 m; Ex: 640 ± 87; Sed-NA: 451 ± 109 m; Ex-NA: 820 ± 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 LNNA-induced lesion formation was reduced by chronic exercise training (Sed, 786 ± 144; Ex, 780 ± 206; Sed-NA, 2,147 ± 522; Ex-NA, 851 ± 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.

Original languageEnglish (US)
Pages (from-to)H535-H540
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number2 54-2
DOIs
StatePublished - Aug 1 2003

Keywords

  • Apolipoprotein E deficiency
  • Atherosclerotic lesions
  • N-nitro-L-arginine
  • Nitric oxide
  • Treadmill

ASJC Scopus subject areas

  • Physiology

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