Ischemia/reperfusion injury (IRI) is the most common cause of early mortality following
lung transplantation (LTx). We hypothesized that
nitrite, an endogenous source of
nitric oxide (NO), may protect lung grafts from IRI. Rat lung grafts were stored in preservation
solution at 4°C for 6 hours. Both grafts and recipients were treated with
nitrite.
Nitrite treatment was associated with significantly higher levels of tissue oxygenation, lower levels of
cytokines and neutrophil/macrophage infiltration, lower
myeloperoxidase activity, reduced oxidative injury and increased cGMP levels in grafts than in the controls. Treatment with either a
nitric oxide scavenger or a
soluble guanylyl cyclase (sGC) inhibitor diminished the beneficial effects of
nitrite and decreased cGMP concentrations. These results suggest that
nitric oxide, generated from
nitrite, is the molecule responsible for the effects of
nitrite via the
nitric oxide/sGC/cGMP pathway.
Allopurinol, a
xanthine oxidoreductase (XOR) inhibitor, abrogated the protective effects of
nitrite, suggesting that XOR is a key
enzyme in the conversion of
nitrite to
nitric oxide. In vitro experiments demonstrated that
nitrite prevented apoptosis in pulmonary endothelial cells.
Nitrite also exhibits longer survival rate in recipients than control. In conclusion,
nitrite inhibits lung IRI following cold preservation and had higher survival rate in LTx model.