NO is an important excitatory neurotransmitter. NO blockers induce marked ventilatory reductions during sustained hypoxia in adult freely-behaving rats. We hypothesized that limited NOS activity may play a role in the biphasic response of developing animals to hypoxia. To test our hypothesis, 3-5-d, 10-d, and 15-d rat pups underwent a 30-min hypoxic challenge (10% O2) before, and following administration of 100 mg/kg N-nitro-L-argine methyl ester (L-NAME), a competitive NOS inhibitor. Ventilation (VE) was measured using whole-body plethysmography. In 15-d hypoxic pups, L-NAME was associated with significantly larger VE reductions when compared to pre-treated animals. In contrast, in 3-5-d pups, VE reductions were similar before, and following L-NAME. Western blots of dorsal brainstem tissue homogenates displayed increasing neuronal NOS expression with increasing postnatal age. These findings suggest that NOS activity mediates excitatory components of the hypoxic ventilatory response. Furthermore, reduced NOS-positive neuronal populations in brainstem respiratory regions may play a role in modulating the biphasic response to hypoxia typically seen in early post-natal life.

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