Asymmetric Dimethylarginine Is Increased in Asthma

• Published in: American journal of respiratory and critical care medicine Vol. 184; no. 7; pp. 779 - 785
• Main Authors: SCOTT, Jeremy A, NORTH, Michelle L, RAFII, Mahroukh, HAILU HUANG, PENCHARZ, Paul, SUBBARAO, Padmaja, BELIK, Jaques, GRASEMANN, Hartmut
• Format: Journal Article
• Language: English
• Published: New York, NY American Thoracic Society 01.10.2011
• Subjects: Adolescent; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Arginine - analogs & derivatives; Arginine - metabolism; Asthma; Asthma - metabolism; Biological and medical sciences; Biomarkers - metabolism; Bronchial Hyperreactivity - metabolism; Case-Control Studies; Child; Chronic obstructive pulmonary disease, asthma; Competition; Disease; Female; Humans; Inflammation; Intensive care medicine; Lungs; Male; Mass spectrometry; Medical sciences; Metabolism; Metabolites; Mice; Mice, Inbred BALB C; Nitric oxide; Nitric Oxide Synthase - metabolism; Pathophysiology; Patients; Pediatrics; Pneumology; Scientific imaging; Smooth muscle; Sputum - metabolism; Steroids; Lung disease; Intensive care; Arginine; Respiratory disease; Aminoacid; Bronchus disease; Obstructive pulmonary disease; Metabolism; biomarker; Resuscitation; Asthma; airways hyperresponsiveness
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201011-1810OC

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor that competes with L-arginine for binding to NOS. It has been suggested that ADMA contributes to inflammation, collagen deposition, nitrosative stress, and lung function in murine models. To test the hypothesis that ADMA is increased in asthma and that NOS inhibition by ADMA contributes to airways obstruction. We assessed alterations of L-arginine, ADMA, and symmetric dimethylarginine (SDMA) levels in a murine model of allergic airways inflammation using LC-tandem mass spectrometry. Based on the levels of ADMA observed in the murine model, we further tested the direct effects of nebulized inhaled ADMA on airways responsiveness in naive control mice. We also assessed alterations of L-arginine, ADMA, and SDMA in humans in adult lung specimens and sputum samples from pediatric patients with asthma. ADMA was increased in lungs from the murine model of allergic airways inflammation. Exogenous administration of ADMA to naive mice, at doses consistent with the levels observed in the allergically inflamed lungs, resulted in augmentation of the airways responsiveness to methacholine. ADMA levels were also increased in human asthma lungs and sputum samples. ADMA levels are increased in asthma and contribute to NOS-related pathophysiology.