Role of nitric oxide synthase/arginase balance in bronchial reactivity in patients with chronic obstructive pulmonary disease
| Autor: | Marc Riquet, Christophe Faisy, Emmanuel Naline, Ingrid Leroy, Dominique Israel-Biet, Marilyne Lévy, Christophe Delclaux, Priscilla Henno, Jean-Marc Tadié, Claire Danel |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male medicine.medical_specialty Benzylamines Physiology Amidines Bronchi Pharmacology Arginine Nitric oxide chemistry.chemical_compound Pulmonary Disease Chronic Obstructive Physiology (medical) Internal medicine medicine Humans Respiratory system Enzyme Inhibitors biology Arginase Dose-Response Relationship Drug business.industry Respiratory disease Cell Biology respiratory system Middle Aged medicine.disease Boronic Acids respiratory tract diseases Nitric oxide synthase Endocrinology NG-Nitroarginine Methyl Ester chemistry biology.protein Cholinergic Female Nitric Oxide Synthase Airway business Acetylcholine medicine.drug |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 294(3) |
| ISSN: | 1040-0605 |
| Popis: | Competition between nitric oxide synthases (NOSs) and arginases for their common substrate l-arginine could be involved in the regulation of cholinergic airway reactivity and subsequent airway remodeling. The aims of this study were to evaluate the relationships between the expression of this enzymatic balance and the effects of NOS and arginase inhibition on bronchoconstrictive response to acetylcholine of patients without and with early chronic obstructive pulmonary disease (COPD). Twenty-two human bronchi [15 COPD (9 GOLD-0, 6 GOLD-1, -2-A), 7 nonsmokers] were investigated for immunohistochemistry and modulation of acetylcholine-induced airway constriction. Significantly increased expression of NOS2 in immunoblots of bronchial tissue and staining in smooth muscle cells was evidenced in patients with COPD compared with control subjects, whereas no modification of arginase expression was evidenced. Forced expiratory volume in 1 s (FEV1) and NOS2 expression were negatively correlated (ρ = −0.54, P = 0.027). Pharmacological experiments demonstrated that resting tension was elevated in COPD compared with control subjects (2,243 ± 154 vs. 1,574 ± 218 mg, P = 0.03) and was positively correlated with the expression of NOS2 (ρ = 0.61, P = 0.044), whereas constrictor response to acetylcholine was similar [active tension, sensitivity (−logEC10), and reactivity (slope)]. The sole effect of the specific arginase inhibitor Nω-hydroxy-nor-l-arginine (1 μM) was to decrease sensitivity in COPD patients, whereas 1 mM NG-nitro-l-arginine methyl ester unexpectedly decreased resting tension because of a non-cGMP-dependent effect. In conclusion, an upregulation of NOS2 expression in COPD patients is involved in airway tone regulation and functional airflow limitation, whereas increased arginase activity is involved in airway sensitivity. |
| Databáze: | OpenAIRE |
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