Respiratory plasticity in response to changes in oxygen supply and demand

Aerobic organisms maintain O2 homeostasis by responding to changes in O2 supply and demand in both short and long time domains. In this review, we introduce several specific examples of respiratory plasticity induced by chronic changes in O2 supply (environmental hypoxia or hyperoxia) and demand (exercise-induced and temperature-induced changes in aerobic metabolism). These studies reveal that plasticity occurs throughout the respiratory system, including modifications to the gas exchanger, respiratory pigments, respiratory muscles, and the neural control systems responsible for ventilating the gas exchanger. While some of these responses appear appropriate (e.g., increases in lung surface area, blood O2 capacity, and pulmonary ventilation in hypoxia), other responses are potentially harmful (e.g., increased muscle fatigability). Thus, it may be difficult to predict whole-animal performance based on the plasticity of a single system. Moreover, plastic responses may differ quantitatively and qualitatively at different developmental stages. Much of the current research in this field is focused on identifying the cellular and molecular mechanisms underlying respiratory plasticity. These studies suggest that a few key molecules, such as hypoxia inducible factor (HIF) and erythropoietin, may be involved in the expression of diverse forms of plasticity within and across species. Studying the various ways in which animals respond to respiratory challenges will enable a better understanding of the integrative response to chronic changes in O2 supply and deman

Ventilatory and Chemoreceptor Responses to Hypercapnia in Neonatal Rats Chronically Exposed to Moderate Hyperoxia

Rats reared in hyperoxia hypoventilate in normoxia and exhibit progressive blunting of the hypoxic ventilatory response, changes which are at least partially attributed to abnormal carotid body development. Since the carotid body also responds to changes in arterial CO2/pH, we tested the hypothesis that developmental hyperoxia would attenuate the hypercapnic ventilatory response (HCVR) of neonatal rats by blunting peripheral and/or central chemoreceptor responses to hypercapnic challenges. Rats were reared in 21% O2 (Control) or 60% O2 (Hyperoxia) until studied at 4, 6–7, or 13–14 days of age. Hyperoxia rats had significantly reduced single-unit carotid chemoafferent responses to 15% CO2 at all ages; CO2 sensitivity recovered within 7 days after return to room air. Hypercapnic responses of CO2-sensitive neurons of the caudal nucleus tractus solitarius (cNTS) were unaffected by chronic hyperoxia, but there was evidence for a small decrease in neuronal excitability. There was also evidence for augmented excitatory synaptic input to cNTS neurons within brainstem slices. Steady-state ventilatory responses to 4% and 8% CO2 were unaffected by developmental hyperoxia in all three age groups, but ventilation increased more slowly during the normocapnia-to-hypercapnia transition in 4-day-old Hyperoxia rats. We conclude that developmental hyperoxia impairs carotid body chemosensitivity to hypercapnia, and this may compromise protective ventilatory reflexes during dynamic respiratory challenges in newborn rats. Impaired carotid body function has less of an impact on the HCVR in older rats, potentially reflecting compensatory plasticity within the CNS