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Published ahead of print on June 19, 2003, doi:10.1165/rcmb.2003-0138OC

Am. J. Respir. Cell Mol. Biol., Volume 29, Number 6, December 2003, 771-778

A more recent version of this article appeared on December 1, 2003
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Submitted on April 18, 2003
Revised on June 19, 2003

Nitric oxide synthases and protein oxidation in the quadriceps femoris of COPD patients

Esther Barreiro1, Joaquim Gea2, Josep M Corominas2, and Sabah N Hussain3*

1 Respiratory Medicine, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain; Medicine, McGill University, Montreal, Quebec, Canada, 2 Respiratory Medicine, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain, 3 Medicine, McGill University, Montreal, Quebec, Canada

* To whom correspondence should be addressed. E-mail: sabah.hussain{at}muhc.mcgill.ca.

Skeletal muscle dysfunction contributes to poor exercise performance in patients with chronic obstructive pulmonary disease (COPD). Increased oxygen radicals and nitric oxide (NO) have been proposed as mechanisms. In this study, we assessed the levels of protein oxidation (carbonyl formation), lipid peroxidation (4-hydroxy-2-nonenal formation), catalase and Mn-superoxide dismutase (Mn-SOD) expressions, nitric oxide synthases (NOSs), and protein tyrosine nitration in quadriceps muscles of 12 COPD patients and 6 control subjects. Lipid peroxidation was elevated in muscles of COPD patients as compared with controls but protein oxidation was not. Muscle Mn-SOD but not catalase protein expression was significantly higher (200%) in COPD patients as compared with control subjects. Expression of neuronal NOS and endothelial NOS isoforms did not differ between controls and COPD patients, whereas no iNOS protein expression was detected in limb muscles of the two groups of subjects. In COPD patients, neuronal NOS expression correlated negatively with the degree of the airway obstruction (%FEV1 predicted). 3-Nitrotyrosine levels were significantly elevated in muscles of COPD patients as compared with control subjects and correlated positively with nNOS protein levels. These results indicate the development of both oxidative and nitrosative stresses in the quadriceps of COPD patients, suggesting their involvement in muscle dysfunction.




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