Midbrain Neurotransmitters in Acute Hypoxic Ventilatory Response
In control ventilation, chemical stimuli are paramount in setting the level of ventilation. These are primarily changes in concentration of hydrogen ions, as well as changes in PO2 and PCO2. A number of receptors, both in the periphery and in the central nervous system, respond to these changes. Of the three socalled “chemical” stimuli, the response to CO2 is most prominent and for any 1 mm change in PCO2, ventilation changes by about 2 to 2.5 L/min. The ventilatory response to hypoxia becomes quite prominent once arterial PO2 has reached values of about 60 mm Hg. It has been well documented that the primary effect of hypoxia is stimulation of the carotid chemoreceptors with transmission of signal to the NTS. With acute hypoxia, there is a biphasic ventilatory response with an initial hyperventilation followed by a fall in ventilation, the so-called “roll-off”, to values above those in the pre-hypoxic level. This biphasic response is present in man as well as in a large number of other mammals tested and central neurotransmitters are essential in this response (4,5,7-10). This presentation will concentrate on the effects of acute hypoxia on the ventilatory response in anesthetized dog and rat, and the relationship between the ventilatory response and the release of neurotransmitters in the central nervous system, but in particular, in the medial chemosensitive area on the ventral surface of the medulla and summarizes the work from our laboratory from the past decade. The amino acids of interest are those that excite ventilation, which are primarily glutamate and aspartate; and those that depress ventilation, which include GABA, taurine, and glycine (3). Earlier work from this laboratory showed that inhibition of glutamate by intravenous administration of the specific NMDA receptor antagonist MK801 in anesthetized dog leads to a significant reduction in the hyperventilatory response to hypoxia (1). The subsequent studies in anesthetized rat showed that ventricular cisternal perfusion of MK801 abolished hyperventilatory response of acute hypoxia and infusion of GABA antagonist bicuculline caused augmentation of the hyperventilatory response to acute hypoxia and the “roll-off” was no longer observed (10).
KeywordsPhrenic Nerve Ventilatory Response Acute Hypoxia Biphasic Response Amino Acid Neurotransmitter
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