doi: 10.1161/CIRCRESAHA.108.191569
© 2009 American Heart Association, Inc.
Letter to the Editor |
When Does Low Oxygen Become Hypoxia? Implications for Nitrite Reduction
Wales Heart Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom, E-mail JamesPP@Cardiff.ac.uk
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
To the Editor:
Webb and Milsom et al1 present the intriguing finding that endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVECs) and potentially RBCs is responsible under hypoxic conditions for nitrite (NO2
) reduction to nitric oxide (NO). Based on several practical and theoretical points of view, the conclusions that the authors draw regarding their data are flawed. It is important that these are considered by the wider Circulation Research readership.
The authors conclude that lack of oxygen (O2) availability to eNOS promotes NO2 reduction to NO. Whereas the RBC experiments involve measurement of NO produced by RBC under nitrogen and acidic conditions, the HUVEC experiments were carried out at 5% O2 and 5% CO2 (refer to online data supplement that accompanies the article for details). Although there is no question 5% O2 is lower than 95% or 21% O2 (typical in vitro experimental/growth conditions), it cannot be accepted that 5% O2 (equating to 
50 µmol/L O2) is "hypoxic" to cells in culture over a 30-minute incubation period. Mitochondrial cytochrome c will function optimally until extremely low O2 conditions (Km0.1 µmol/L),2 and perhaps more importantly eNOS functions optimally with a Km6 to 9 µmol/L.3–4 Limited O2 availability to eNOS is unlikely the cause of the change that the authors have observed under these experimental conditions. The thrust of the article (ie, the reduction of NO2 to NO during hypoxia by eNOS) is not valid for HUVECs.
A second issue relates to