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Nitric Oxide Synthases and Protein Oxidation in the Quadriceps Femoris of Patients with Chronic Obstructive Pulmonary Disease

Critical Care and Respiratory Divisions, Royal Victoria Hospital and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada; and Muscle Research Unit, Departments of Respiratory Medicine and Pathology, IMIM-Hospital del Mar, Universitat Pompeu Fabra & Universitat Autònoma, Barcelona, Catalonia, Spain

Address correspondence to: Dr. S. Hussain, Room L3.05, 687 Pine Ave. West, Montreal, PQ, H3A 1A1 Canada. 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 patients with patients with COPD and 6 control subjects. Lipid peroxidation was elevated in muscles of patients with patients with COPD as compared with control subjects, but protein oxidation was not. Muscle Mn-SOD but not catalase protein expression was significantly higher (200%) in patients with patients with COPDas compared with control subjects. Expression of neuronal NOS and endothelial NOS isoforms did not differ between control subjects and patients with COPD, whereas no inducible NOS protein expression was detected in limb muscles of the two groups of subjects. In patients with COPD, neuronal NOS expression correlated negatively with the degree of the airway obstruction (%FEV₁ predicted). 3-Nitrotyrosine levels were significantly elevated in muscles of patients with COPDas 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 patients with COPD, suggesting their involvement in muscle dysfunction.

Abbreviations: body mass index, BMI • chronic obstructive pulmonary disease, COPD • carbon monoxide trasfer, DL_CO • endothelial nitric oxide synthase, eNOS • 4-Hydroxy-2-nonenal, HNE • high-performance liquid chromatography, HPLC • horseradish peroxidase, HRP • inducible nitric oxide synthase, iNOS • manganese superoxide dismutase, Mn-SOD • myosin heavy chain, MyHC • neuronal nitric oxide synthase, nNOS • nitric oxide, NO • nitric oxide synthase, NOS • optical density, OD • reactive oxygen species, ROS • maximal oxygen uptake, O₂max • maximal mechanical power output, W_max

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