Excitatory and Inhibitory Influences on the Ventilatory Augmentation Caused by Hypoxia

Maintenance of an adequate supply of O2 to tissues depends on a complex pattern of circulatory and ventilatory adjustments that are triggered by environmental perturbations, alterations in arterial O2 levels, and changes in metabolic rate (16, 17, 66). Ventilatory responses to hypoxia are mediated by discrete neural pathways involving peripheral chemoreceptors, primary afferents, and central neurons (16, 17, 66). Hypoxia increases ventilation entirely by its effects on the peripheral chemoreceptors, mainly the carotid body (17, 18, 51, 63, 66). The characteristics of the response, however, depend on complex interactions at multiple levels of the neuraxis, including the primary afferent neurons and bulbopontine pathways through which the carotid body signals are processed and transduced to ventilation. Neurons in the nucleus of the tractus solitarius and near the ventrolateral surface of the medulla, for example, particularly in the nucleus paragigantocellularis lateralis, play a pivotal role in amplifying respiratory responses to hypercapnia and hypoxia (8, 38, 50, 62). Moreover, hypoxia can affect breathing by direct actions on the brain, including alterations in cerebral blood flow, stimulation or depression of diencephalic and cortical neurons, and possibly changes in cerebral metabolism (16–18, 54, 66).