Influence of oxygen, temperature and carbon dioxide on nitric oxide formation from nitrite as measured in expired gas from in situ perfused rabbit lungs

In biological systems, nitric oxide (NO) may be generated non-enzymatically from nitrite (nitrite-derived NO), in addition to nitric oxide synthase-catalyzed (NOS-derived) l-arginine-dependent formation. Through recordings of expired NO, we studied the influence of temperature on NOS- and nitrite-derived NO in the perfused lung. We also studied the impact of other influencing factors (O2, CO2, and pH) on nitrite-derived NO in the same system. Both NO-generating systems exhibited biphasic temperature dependence with a positive correlation between temperature and NO generation that peaked between 42 and 44 °C. The nitrite-derived NO generation was enhanced by hypoxia alone (> 20× after 5 min) and further by concomitant increase in CO2. The CO2 effect could not be explained by changes in extracellular pH and was unaltered by acetazolamide. We conclude that the temperature dependence in the known enzyme-catalyzed NOS-derived NO and especially in the nitrite-derived NO strengthens the hypothesis that an enzyme could be involved in nitrite-derived NO formation. The enhancement of nitrite-derived NO by increases in CO2 suggests that this system could be of importance to improve perfusion in ischemic tissues.