Superoxide dismutase-1 influences the timing and post-hypoxic stability of neonatal breathing

Reactive oxygen species (ROS) likely play a role in the hypoxic ventilatory response. We determined whether hypoxic responses were influenced by alterations in cellular redox status induced by reductions in superoxide dismutase-1 (SOD-1) activity, a cytosolic anti-oxidant enzyme. Using whole-body, continuous-flow plethysmography, we compared ventilatory responses to moderate hypoxia (10% inspired O2) of Sod1+/+, +/- and -/- postnatal day 4 (P4) littermates. Sod1+/- neonates exhibited a consistently lower breathing frequency than their wild-type littermates, regardless of inspired O2 level. While SOD-1 deficiency had no effect on the magnitude of the ventilatory response during hypoxia, it did compromise stability of breathing in the post-hypoxic period. Our results suggest SOD-1 stimulates ventilation and helps stabilize breathing after a hypoxic perturbation.