Moderate elevations of
nitrite and
nitric oxide (NO) protect mammalian tissues against
ischemia (
anoxia)-
reperfusion damage by inhibiting mitochondrial electron transport complexes and reducing the formation of
reactive oxygen species (ROS) upon reoxygenation. Crucian carp appear to exploit this mechanism by upregulating
nitrite and other
nitrite/NO metabolites (S-nitroso and
iron-nitrosyl compounds) in several tissues when exposed to
anoxia. We investigated whether this is a common strategy amongst
anoxia-tolerant vertebrates by evaluating NO metabolites in red-eared slider turtles during long-term (9 days)
anoxia and subsequent reoxygenation at low temperature, a situation naturally encountered by turtles in
ice-covered ponds. We also measured
glutathione in selected tissues and assessed the impact of
anoxia on
electrolyte status.
Anoxia induced major increases in [
nitrite] in the heart, pectoral muscle and red blood cells, while [
nitrite] was maintained unaltered in brain and liver. Concomitantly, the concentrations of S-nitroso and
iron-nitrosyl compounds increased, showing that
nitrite was used to produce NO and to S-nitrosate cellular molecules during
anoxia. The changes were gradually reversed during reoxygenation (1 h and 24 h), testifying that the processes were reversible. The increased NO bioavailability occurred in the absence of
NO synthase activity (due to global
anoxia) and may involve mobilization of internal/external
nitrite reservoirs. Our data support the theory that anoxic upregulation of
nitrite and other NO metabolites could be a general cytoprotective strategy amongst
anoxia-tolerant vertebrates. The possible mechanisms of
nitrite-derived NO and S-nitrosation in protecting cells from destructive Ca(2+) influx during
anoxia and in limiting ROS formation during reoxygenation are discussed.