Different Disappearance Rates of Plasma Nitrite (NO2-) Contribute to Apparent Steady-State Arterio-Venous Differences in Anesthetized Animals

: A possible cause of arterio-venous (A-V) differences in plasma nitrite (NO(2)(-)) levels under steady-state conditions and kinetic features of NO(2)(-) in arterial and venous blood were examined. In isolated rabbit blood, plasma NO(2)(-) in venous blood disappeared faster than that in arterial blood and was accompanied by a concomitant increase in nitrate (NO(3)(-)), implicating oxidation as the main pertinent metabolic pathway. When data were corrected with respective elimination constants and time durations before plasma separation, no A-V difference was estimated under steady-state. Even after these corrections for NO(2)(-) loading in anesthetized rabbits, a large A-V difference in NO(2)(-) levels (arterial venous) was observed, followed by an exponential decrease in NO(2)(-) levels without a reciprocal increase in NO(3)(-) levels. There was a marked difference in NO(2)(-) decay between in vivo and ex vivo experiments, but no increases in the circulating blood were detected for other substances derived from NO(2)(-), such as methemoglobin or low- and high-molecular weight nitrosothiols. In rats and guinea pigs, absence and presence of the A-V difference were detected under steady-state conditions and after NO(2)(-) loading, respectively. These observations indicate that apparent A-V differences under steady-state are artifacts arising from different rates of NO(2)(-) disappearance in arterial versus venous plasma during sample handling, and that tissue compartments may contribute to changes in NO(2)(-) levels in circulating blood. Therefore, caution is required when evaluating plasma NO(2)(-) levels, especially in venous blood.