NMDA glutamate receptor antagonism and the ventilatory response to hypoxia in the anesthetized rat

This study seeks to discern the influence of the NMDA glutamate-mediated pathway in the early stimulatory and late depressant phases of the hypoxic ventilatory response. We addressed this issue by recording ventilation before and after intravenous administration of the NMDA receptor antagonist MK-801 during acute, steady-state hypoxic challenges in the anesthetized, spontaneously breathing rats. Minute ventilation and its volume and frequency components were calculated and compared at the peak and nadir of the hypoxic response. We found that NMDA receptor antagonism appreciably affected both ventilatory phases of hypoxia. The early stimulation of ventilation was attenuated and the late depression was accentuated. The latter consisted of abolishment of the characteristic sustenance of hypoxic ventilation above the baseline level in the depressant phase, so that ventilation declined down to the baseline after NMDA receptor blockade. The inability to uphold ventilation in the depressant phase suggests that the NMDA glutamate-mediated pathway is operative in shaping the late hypoxic ventilatory response. The role of the glutamatergic pathway may thus be extended beyond the hitherto recognized early ventilatory stimulation of hypoxia.