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Am J Physiol Lung Cell Mol Physiol 284: L452-L457, 2003. First published November 15, 2002; doi:10.1152/ajplung.00270.2002
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Vol. 284, Issue 3, L452-L457, March 2003

Regulation of nitric oxide production in limb and ventilatory muscles during chronic exercise training

T. Vassilakopoulos1, G. Deckman2, M. Kebbewar1, G. Rallis1, R. Harfouche1, and S. N. A. Hussain1

1 Critical Care and Respiratory Divisions, McGill University Health Center and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada H3A 1A1; and 2 Department of Physical Therapy, Husson College, Bangor, Maine 04401

In this study, we evaluated the differential influence of chronic treadmill training (30 m/min, 15% incline, 1 h/day, 5 days/wk) on nitric oxide (NO) production and NO synthase (NOS) isoform expression as well as 3-nitrotyrosine formation (footprint of peroxynitrite) both in limb (gastrocnemius) and ventilatory (diaphragm) muscles. A group of exercise-trained rats and a control group (no training) were examined after a 4-wk experimental period. Exercise training elicited an approximate fourfold rise in gastrocnemius NOS activity and augmented protein expression of the endothelial (eNOS) and neuronal (nNOS) isoforms of NOS to ~480% and 240%, respectively. Qualitatively similar but quantitatively smaller elevations in NOS activity and eNOS and nNOS expression were observed in the diaphragm. No detectable inducible NOS (iNOS) protein expression was found in any of the muscle samples. Training increased the intensity of 3-nitrotyrosine only in the gastrocnemius muscle. We conclude that whole body exercise training enhances both limb and ventilatory muscle NO production and that constitutive and not iNOS isoforms are responsible for increased protein tyrosine nitration in trained limb muscles.

skeletal muscle; peroxynitrite; oxygen radicals


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