title: Central amino acid neurotransmitters and the hypoxic ventilatory response.
abstract: Acute sustained hypoxia causes an early rise in ventilation, followed by a reduction in ventilation ("roll off") after several minutes to levels below the peak but above baseline. The underlying mechanism(s) of this biphasic response is unclear. Hypoxia induces changes in the release and metabolic turnover of glutamate and gamma aminobutyric acid (GABA). These endogenous neuroactive agents may play a role in mediating the biphasic hypoxic ventilatory response. Therefore, their role was studied in anesthetized (isoflurane), isocapnic, mechanically ventilated rats. Hypoxia alone (FIO2 = 0.1) produced the characteristic biphasic response in the phrenic neurogram (n = 6). When the glutamate receptor was blocked with application of two different N-methyl-D-aspartate (NMDA) antagonists, MK-801 or AP-5, to the ventrolateral medullary surface (VMS), the phrenic output fell by 90% during normoxia and demonstrated no response to hypoxia (n = 6 for each group). There was a rise of 60% in phrenic nerve output during normoxia when GABA antagonist bicuculline was applied to the VMS, and with hypoxia it rose another 15%, and no fall off was seen during hypoxia (n = 6). These findings suggest that during hypoxia the initial hyperventilation has a glutamatergic component and the subsequent fall off its mediated by GABAergic mechanisms.
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston.
authors.forename: I
authors.initials: I
authors.lastname: Soto-Arape
authors.forename: M D
authors.initials: MD
authors.lastname: Burton
authors.forename: H
authors.initials: H
authors.lastname: Kazemi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010791:Phrenic Nerve / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid