Role of glutamate as the central neurotransmitter in the hypoxic ventilatory response

Abstract

Recent data suggest that the increase in ventilation during hypoxia may be related to the release of the excitatory amino acid neurotransmitter glutamate centrally. To further investigate this, we studied the effects of MK-801, a selective noncompetitive N-methyl-D-aspartate receptor antagonist, on the hypoxic ventilatory response in lightly anesthetized spontaneously breathing intact dogs. The cardiopulmonary effects of sequential ventriculocisternal perfusion (VCP) at the rate of 1 ml/min with mock cerebrospinal fluid (CSF, control) and MK-801 (2 mM) were compared during normoxia and 8 min of hypoxic challenge with 12% O2. Minute ventilation (VE), tidal volume (VT), and respiratory frequency (f) were recorded continuously, and hemodynamic parameters [heart rate (HR), blood pressure (MAP), cardiac output (CO), pulmonary arterial pressure, and pulmonary capillary wedge pressure] were measured periodically. Each dog served as its own baseline control before and after each period of sequential VCP under the two different O2 conditions. During 15 min of normoxia, there were no significant changes in the cardiopulmonary parameters with mock CSF VCP, whereas with MK-801 VCP for 15 min, VE decreased by approximately 27%, both by reductions in VT and f (17 and 9.5%, respectively). HR, MAP, and CO were unchanged. During 8 min of hypoxia with mock CSF VCP, VE increased by 171% associated with increased VT and f (25 and 125%, respectively). HR, MAP, and CO were likewise augmented. In contrast, the hypoxic response during MK-801 VCP was characterized by an increased VE of 84%, mainly by a rise in f by 83%, whereas the VT response was abolished. The cardiovascular excitation was also inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Apnea of prematurity: pathogenesis and management strategies

“…N-methyl D-aspartate glutamate receptors in the nucleus of the solitary tract have a pivotal role in the hypoxic ventilatory response. 12 Preterm infants exhibit a biphasic ventilatory response. 13 There is an initial increase in ventilation for approximately 1 min.…”

NMDA receptor-mediated modulation of ventilation in obese Zucker rats

“…12,13,24,27 For the current study, however, we selected dextromethorphan (DM) over MK-801 because preliminary studies in our lab demonstrated that low doses of MK-801 (0.1 ± 0.5 mgakg, i.p.) produced restlessness and hyperlocomotion in Z rats, while higher doses of MK-801 (1 ± 5 mgakg, i.p.)…”

Effect of Amino Acid Infusion on the Ventilatory Response to Hypoxia in Protein-Deprived Neonatal Piglets

“…The AA solution used in this study contained proportionally more excitatory AA such as glutamate and aspartate than inhibitory AA such as glycine. which may also have an influence on the ventilatory response to hypoxia (5,30,31). Furthermore, the fact that this AA solution docs not contain GABA, an important inhibitory ncurotransmitter, may facilitate the effects of excitatory AA on the central respiratory system.…”

“…Some of these changes may be mediated by the increase and/or decrease in inhibitory or excitatory neurotransmitters in the CNS (4,10). One of the latter is glutamate, a central excitatory neurotransmitter that participates in the ventilatory response to hypoxia (5). Other AA that are not neurotransmitters may also influence the central respiratory output.…”