Brain glutamate metabolism during hypoxia and peripheral chemodenervation.
Glutamate stimulates resting ventilation by altering neural excitability centrally. Hypoxia increases central ventilatory drive through peripheral chemoreceptor stimulation and may also alter cerebral perfusion and glutamate metabolism locally. Therefore the effect of hypoxia and peripheral chemodenervation on cerebrospinal fluid (CSF) transfer rate of in vivo tracer amidated central nervous system glutamate was studied in intact and chemodenervated pentobarbital-anesthetized dogs during normoxia and after 1 h of hypoxia induced with 10 or 12% O2 in N2 breathing at constant expired ventilation and arterial CO2 tension. Chemodenervation was performed by bilateral sectioning of the carotid body nerves and cervical vagi. CSF transfer rates of radiotracer 13NH4+ and [13N]glutamine synthesized via the reaction, glutamate + NH4(+)----glutamine, in brain glia were measured during normoxia and after 1 h of hypoxia. At normoxia, maximal glial glutamine efflux rate jm = 103.3 +/- 11.2 (SE) mumol.l-1.min-1 in all animals. After 1 h of hypoxia in intact animals, jm = 78.4 +/- 10.0 mumol.l-1.min-1. In denervated animals, jm was decreased to 46.3 +/- 4.3 mumol.l-1.min-1. During hypoxia, mean cerebral cortical glutamate concentration was higher in denervated animals (9.98 +/- 1.43 mumol/g brain tissue) than in intact animals (7.63 +/- 1.82 mumol/g brain tissue) and corresponding medullary glutamate concentration tended to be higher in denervated animals. There were no differences between mean glutamine and gamma-aminobutyric acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Hoop
B
B
Medical Services (Pulmonary and Critical Care Unit), Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Masjedi
M R
MR
Shih
V E
VE
Kazemi
H
H
D000136:Acid-Base Equilibrium / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000502:physiology*; D003714:Denervation; D004285:Dogs; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006439:Hemodynamics / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D012119:Respiration / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005971:Glutamates; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid