In vivo release of glutamate in nucleus tractus solitarii of the rat during hypoxia.
1. An attempt has been made to test the hypothesis that, in the caudal part of nucleus tractus solitarii (NTS) where carotid sinus nerve (CSN) afferents project, L-glutamate (Glut) modulates the hypoxic ventilatory response. 2. Unanaesthetized, peripherally chemodenervated (carotid body denervated; CBD) and sham-operated, freely moving rats were used. During peripheral chemoreceptor stimulation by hypoxia (10% O2 for 30 min) or doxapram (Dox) infusion (2 mg kg-1 (30 min)-1), ventilation was recorded and successively, under the same conditions, the extracellular Glut concentration ([Glut]o) in the caudal NTS was measured by in vivo microdialysis. [Glut]o was also measured during hyperoxic hypercapnia (10% CO2-30% O2 for 30 min). 3. Furthermore, the effects on ventilation of exogenous Glut, the NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 or the ionotropic receptor antagonist kynurenate microinjected into the caudal NTS were investigated in sham-operated rats. 4. In sham-operated rats, both ventilation and [Glut]o in NTS were increased during peripheral chemoreceptor stimulation. On the other hand, no increases in either ventilation or Glut release were observed in CBD rats. In spite of ventilatory augmentation during hypercapnia, no response of [Glut]o to hypercapnia was observed in either group. 5. Local Glut application into NTS increased ventilation. Pretreatment with MK-801 or kynurenate reduced the hypoxic ventilatory response. This reduction in ventilation was mainly due to the decrease in tidal volume. 6. These results suggest that hypoxia induced the release of Glut in NTS and that this effect was mediated by arterial chemosensory input.
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
A
A
Mizusawa
H
H
Ogawa
Y
Y
Kikuchi
W
W
Hida
H
H
Kurosawa
S
S
Okabe
T
T
Takishima
K
K
Shirato
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002344:Carotid Body / Q000502:physiology; D002628:Chemoreceptor Cells / Q000502:physiology; D003714:Denervation; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D004315:Doxapram / Q000008:administration & dosage / Q000494:pharmacology; D018698:Glutamic Acid / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D004315:Doxapram; D007736:Kynurenic Acid