Differential sensitivity to hypoxic inhibition of respiratory processes in the anesthetized rat.

To estimate the sensitivity to hypoxic inhibition of various regulatory processes for respiration, changes in breathing pattern during hypoxic ventilatory depression (HVD) were analyzed in the halothane-anesthetized spontaneously breathing rat using a "progressive isocapnic hypoxia test." In the carotid sinus nerve (CSN) intact rats, ventilatory augmentation was followed by depression due to reduction in respiratory frequency (f) at end-tidal PO2 (PETO2) levels below 50-60 mmHg despite increased afferent activities from the carotid chemoreceptors. After CSN section, ventilation was progressively depressed at PETO2 lower than normoxic level with simultaneous decreases of f and tidal volume. An increase in CO2 stimulus or the prevention of arterial hypotension during hypoxia by infusing a vasoconstrictor agent (phenylephrine) inhibited the occurrence of ventilatory depression in both the CSN intact and denervated animals. In all cases studied, the reduction in f resulted mainly from the prolongation of expiratory time (TE). The results suggest that in the anesthetized rat the effect of respiratory stimulation from carotid chemoreceptor afferents becomes inadequate to offset the prolongation of TE due to the central hypoxia at lower PETO2, and that the neural process for regulating TE is the major site of deterioration during central hypoxic inhibition. Roles of CO2 stimulus and systemic circulatory conditions in the generation of HVD were also discussed.