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Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
NMDA glutamate receptor antagonism and the ventilatory response to hypoxia in the anesthetized rat
I Tarakanov1, A Dymecka, M Pokorski
1Laboratory of Ventilation Pathology, Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow, Russia.
Abstract:
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.
Insights
The NMDA glutamate pathway influences breathing during hypoxia. Blocking NMDA receptors with MK-801 attenuated early breathing stimulation and worsened late breathing depression in rats.
Area of Science:
- Neuroscience
- Respiratory Physiology
Background:
- The hypoxic ventilatory response (HVR) is crucial for maintaining oxygen levels.
- The role of the N-methyl-D-aspartate (NMDA) glutamate pathway in HVR is not fully understood.
Purpose of the Study:
- To investigate the influence of the NMDA glutamate-mediated pathway on both early stimulatory and late depressant phases of the hypoxic ventilatory response.
Main Methods:
- Anesthetized, spontaneously breathing rats were subjected to acute hypoxic challenges.
- Ventilation was recorded before and after intravenous administration of the NMDA receptor antagonist MK-801.
- Minute ventilation, tidal volume, and breathing frequency were analyzed at peak and nadir of the HVR.
Main Results:
- NMDA receptor antagonism with MK-801 attenuated the early stimulation of ventilation during hypoxia.
- NMDA receptor blockade accentuated the late depressant phase of HVR.
- Ventilation declined to baseline levels after MK-801, indicating an inability to sustain hypoxic ventilation.
Conclusions:
- The NMDA glutamate-mediated pathway plays a significant role in shaping the late, depressant phase of the hypoxic ventilatory response.
- The glutamatergic pathway's function in HVR extends beyond early stimulation, impacting ventilatory control during sustained hypoxia.
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