Author(s)

Jia Liu, Jun Wang, Ah Siew Sim, Nitin Mohan, Sharron Chow, Deborah H. Yates, Xingli Wang, Paul S. Thomas

Cardiovascular Genetics Laboratory, Prince of Wales Hospital, Sydney, Australia.
Department of Thoracic Medicine, St. Vincent’s Hospital, Sydney, Australia.
Division of Cardiothoracic Surgery, Texas Heart Institute at St. Luke’s Episcopal Hospital,Baylor College of Medicine, Houston, USA.
Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Respiratory Medicine, Prince of Wales Hospital, Sydney, Australia.
School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.

Background and Objectives: Exhaled nitric oxide (NO) is decreased by smoking while oxides of nitrogen such as nitrites/nitrates (NO_x) are increased. It was hypothesised that in vitro cigarette smoke extract (CSE) would either inhibit NO generation by increasing the NO synthase inhibitor, NG, NG-dimethyl-L-arginine (ADMA) or increase NO_x levels via an oxidation pathway, which in turn could be inhibited by the antioxidant N-acetylcysteine NAC. Methods: Transformed airway cells (A549) were cultured with control medium, 1.0% CSE in culture medium, or 0.8 mM NAC with 1.0% CSE. Baseline L-arginine, NO_x and ADMA levels were measured in the media. Conditioned media were then sampled at 1hour, 6 hours, 24 hours, 48 hours and 72 hours after incubation. Results: CSE induced significantly higher NO_x levels (mean (SD) peak increase of 135.8 (126.6)% after incubation for 6 hours (p < 0.0005)). NAC pre-treatment partially reversed this effect to 35.6 (21.4)% at 6 hours (p = 0.009). ADMA levels were significantly higher in the CSE conditioned media compared with control media (p = 0.02) while NAC pre-treatment did not affect ADMA levels. Conclusions: CSE increased NO_x which was partially reversed by NAC pre-treatment. ADMA levels were also increased after CSE exposure, suggesting that it activates the NO pathway via oxidative-stress while inhibition probably occurs via both ADMA and NOS.

Airway; Cigarette; Nitric Oxide; Nitric Oxide Synthase; N-Acetylcysteine; NG; NG-Dimethyl-L-Arginine

J. Liu, J. Wang, A. Sim, N. Mohan, S. Chow, D. Yates, X. Wang and P. Thomas, "Regulation of Nitric Oxide by Cigarette Smoke in Airway Cells," Open Journal of Respiratory Diseases, Vol. 2 No. 1, 2012, pp. 9-16. doi: 10.4236/ojrd.2012.21002.