European Journal of Applied Physiology

, Volume 112, Issue 2, pp 677–687 | Cite as

The role of nitric oxide in cellular response to hyperbaric conditions

  • Kyriaki Venetsanou
  • George Fildissis
  • Rea Tokta
  • Christos Brinias
  • George Baltopoulos
Original Article


Nitric oxide (NO) acts as a regulator in cell proliferation and expression of growth factors and forms peroxynitrite (ONOO) in oxidative conditions. The aim of the study was to investigate the role of NO in cellular response to hyperbaric oxygen (HBO). NO and nitrotyrosine (NT), biochemical marker for ONOO, cell proliferation and growth factors, were ex-vivo studied in cell cultures under HBO and normobaric (NOR) conditions. A549 (epithelial), L929 (fibroblast) and SVEC (endothelial) were exposed to 100% O2, at P = 280 kPa for t = 60 min, once daily for five sessions. Cell proliferation was determined as the incorporation of bromodeoxyuridine (BrdU) into cells and NO as nitrates/nitrites (NO3 / NO2 ) Gries reaction product in cell culture supernatant (CCSP). NT, vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGFb1) were measured with enzyme-inked immunosorbent assay (ELISA) in CCSP. The time course of total NO was opposite to that of cell proliferation in HBO conditions, peaking after the second HBO session, while cell proliferation showed a reverse trend, minimizing at the same time, suggesting a reverse and transient anti-proliferative effect. Released growth factors were significantly increased in late HBO sessions. NT peaked after second treatment, indicating the formation of ONOO. In control cultures (NOR), proliferation rate was downward and no significant differences were found for the other parameters. In conclusion, the data suggested a key role for NO in the beneficial HBO action, depending on its concentration, which fluctuated with the time of HBO exposure and the activation of oxidant–antioxidant (REDOX) mechanisms, regardless of cell type.


Hyperbaric oxygen (HBO) Nitric oxide Cell proliferation Oxidative stress Growth factors 



We thank Professor J. I. Sznajder (Northwestern University, Chicago USA), Professor Sadis Matalon (University of Alabama at Birmingham, USA), Professor C. Sekeris (Medical School, University of Athens, Greece) and Professor A. Papapetropoulos (Nursing School University of Athens, Greece) for the kindly offered cell lines. The project was provided a partial grant from the Athens University and supported by the KAT Hospital.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Kyriaki Venetsanou
    • 1
  • George Fildissis
    • 1
  • Rea Tokta
    • 1
  • Christos Brinias
    • 1
  • George Baltopoulos
    • 1
  1. 1.Athens University Faculty of Nursing, Hyperbaric Oxygen Therapy Unit and Research Unit at ‘KAT’ General HospitalAthensGreece

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