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Int. J. Mol. Sci. 2014, 15(4), 6062-6071; doi:10.3390/ijms15046062

Asymmetric Dimethylarginine in Chronic Obstructive Pulmonary Disease (ADMA in COPD)

1 Department of Health Sciences, Lakehead University, 955 Oliver Road, Thunder Bay, ON P7B 5E1, Canada 2 Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada 3 Department of Physiology and Biophysics, Boston University School of Medicine, 72 East Concord St., Boston, MA 02118, USA 4 Program in Physiology and Experimental Medicine, SickKids Research Institute, and Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, 555 University Avenue University of Toronto, Toronto, ON M5G 1X8, Canada
* Author to whom correspondence should be addressed.
Received: 30 December 2013 / Revised: 7 March 2014 / Accepted: 31 March 2014 / Published: 10 April 2014
(This article belongs to the Special Issue ADMA and Nitrergic System)
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l-Arginine metabolism including the nitric oxide (NO) synthase and arginase pathways is important in the maintenance of airways function. We have previously reported that accumulation of asymmetric dimethylarginine (ADMA) in airways, resulting in changes in l-arginine metabolism, contributes to airways obstruction in asthma and cystic fibrosis. Herein, we assessed l-arginine metabolism in airways of patients with chronic obstructive pulmonary disease (COPD). Lung function testing, measurement of fractional exhaled NO (FeNO) and sputum NO metabolites, as well as quantification of l-arginine metabolites (l-arginine, l-ornithine, l-citrulline, ADMA and symmetric dimethylarginine) using liquid chromatography-mass spectrometry (LC-MS) were performed. Concentrations of l-ornithine, the product of arginase activity, correlated directly with l-arginine and ADMA sputum concentrations. FeNO correlated directly with pre- and post-bronchodilator forced expiratory volume in one second (FEV1). Sputum arginase activity correlated inversely with total NO metabolite (NOx) and nitrite concentrations in sputum, and with pre- and post-bronchodilator FEV1. These findings suggest that ADMA in COPD airways results in a functionally relevant shift of l-arginine breakdown by the NO synthases towards the arginase pathway, which contributes to airway obstruction in these patients.
Keywords: arginine metabolism; nitric oxide; asymmetric dimethylarginine; arginase; pulmonary function; airway obstruction; l-ornithine arginine metabolism; nitric oxide; asymmetric dimethylarginine; arginase; pulmonary function; airway obstruction; l-ornithine
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Scott, J.A.; Duongh, M.; Young, A.W.; Subbarao, P.; Gauvreau, G.M.; Grasemann, H. Asymmetric Dimethylarginine in Chronic Obstructive Pulmonary Disease (ADMA in COPD). Int. J. Mol. Sci. 2014, 15, 6062-6071.

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