Absence of MK801-induced inspiratory prolongation in chronically hypoxic rats.

N-methyl-D-aspartate (NMDA) receptors play important roles in the neural control of respiration. We hypothesized that the brainstem circuit for respiratory control is modulated in response to chronic hypoxia during postnatal maturation, and the modulation may involve changes in the neurotransmission mediated by the NMDA receptors for inspiratory termination. Electrophysiological studies were performed on anesthetized, vagotomized, paralyzed and ventilated rats. Phrenic nerve activity was recorded in normoxic control and chronically hypoxic (CH) rats maintained in normobaric hypoxia (10% O2) for 4-5 weeks from birth. In normoxic rats, the NMDA receptor antagonist, dizocilpine (MK801, i.p.) irreversibly increased inspiratory time (Ti) by 53% and decreased expiratory time (Te) by 29%. However, MK801 did not change the Ti, Te, respiratory rate and peak phrenic nerve activity in CH rats. Results suggest that brainstem mechanisms underlying inspiratory termination mediated by NMDA receptors are modulated by early chronic hypoxia.