title: Asymmetric dimethylarginine is increased in asthma.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To test the hypothesis that ADMA is increased in asthma and that NOS inhibition by ADMA contributes to airways obstruction.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  ADMA levels are increased in asthma and contribute to NOS-related pathophysiology.
authors: Division of Occupational Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Jeremy A
authors: JA
authors: Scott
authors: Michelle L
authors: ML
authors: North
authors: Mahroukh
authors: M
authors: Rafii
authors: Hailu
authors: H
authors: Huang
authors: Paul
authors: P
authors: Pencharz
authors: Padmaja
authors: P
authors: Subbarao
authors: Jaques
authors: J
authors: Belik
authors: Hartmut
authors: H
authors: Grasemann
mesh_terms: D000293:Adolescent; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000378:metabolism; D013183:Sputum / Q000378:metabolism
chemical_list: D015415:Biomarkers; C487735:dimethylarginine; C024917:symmetric dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase