Xanthine oxidoreductase-catalyzed reduction of nitrite to nitric oxide: Insights regarding where, when and how

► Xanthine oxidoreductase (XOR) catalyzes NO formation from NO2- under anoxia. ► Inhibition of XOR diminishes beneficial outcomes mediated by NO2- treatment. ► However, inhibition of XOR produces salutary outcomes in similar models. ► The in vivo significance of XOR-derived NO formation from NO2- is thus unclear. ► We critically review key factors that combine to “switch” XOR from oxidant to NO production.