Effects of Aminoguanidine, an Inhibitor of Inducible Nitric Oxide Synthase, on Nitric Oxide Production and Its Metabolites in Healthy Control Subjects, Healthy Smokers, and COPD Patients
| Autor: | Peter J. Barnes, Kazuhiro Ito, Caterina Brindicci, Olga Torre, Sergei A. Kharitonov |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.medical_specialty Pathology Nitric Oxide Synthase Type II Nitric Oxide Critical Care and Intensive Care Medicine Endothelial NOS Guanidines Bronchial Provocation Tests Nitric oxide Pulmonary Disease Chronic Obstructive chemistry.chemical_compound Double-Blind Method Reference Values Internal medicine Administration Inhalation Humans Medicine Exhaled breath condensate Reactive nitrogen species Aged COPD Cross-Over Studies biology business.industry Nebulizers and Vaporizers Nitrotyrosine Smoking Sputum Middle Aged medicine.disease Pimagedine Respiratory Function Tests respiratory tract diseases Nitric oxide synthase Oxidative Stress Treatment Outcome Endocrinology chemistry biology.protein Female Cardiology and Cardiovascular Medicine business Biomarkers |
| Zdroj: | Chest. 135:353-367 |
| ISSN: | 0012-3692 |
| Popis: | Background Nitric oxide (NO) is produced by resident and inflammatory cells in the respiratory tract by the enzyme NO synthase (NOS), which exists in three isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS. NO production is increased in patients with COPD, and the production of NO under oxidative stress conditions generates reactive nitrogen species that may amplify the inflammatory response in COPD. Methods To examine the role of increased NO in COPD, we administered a relatively selective iNOS inhibitor, aminoguanidine, by nebulization in a double-blind, placebo-controlled study in COPD patients, healthy smokers, and healthy nonsmoking subjects. We investigated whether aminoguanidine had any effect on exhaled NO produced in the central lung (flux of NO from the airways [J no ] and peripheral lungs (concentration of NO in peripheral lung [C alv ], on NO metabolites (nitrite [NO 2 − ]/nitrate [NO 3 − ], peroxinitrite [ONOO − ], nitrotyrosine), and on a marker of oxidative stress (8-isoprostane) in exhaled breath condensate (EBC) and in sputum. Results Aminoguanidine administration resulted in a significant reduction in J no compared with administration of the saline solution control in healthy subjects, smokers, and COPD patients. C alv in smokers and in COPD patients was not completely inhibited 1 h after aminoguanidine inhalation, in marked contrast to previous results in asthma. Moreover, ONOO − and NO 2 − /NO 3 − levels were also increased in EBC and in sputum of smokers and COPD and were not completely inhibited following aminoguanidine inhalation. 8-Isoprostane levels were also increased in smokers and in COPD patients but were not reduced after aminoguanidine inhalation. Conclusions These results suggest that the constitutive NOS isoform as well as iNOS might be involved in NO release and contribute to the high C alv and ONOO − production in patients with COPD. Trial registration: Clinicaltrials.gov Identifier: NCT00180635. |
| Databáze: | OpenAIRE |
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