The proposed research is designed to gain a better understanding of the regulation of central nervous system (CNS) acid-base and electrolyte homeostasis. The CNS acid-base status, in turn, has an important effect on the central chemical ventilatory drive. Regulation of the cerebrospinal fluid (CSF) chloride concentration likely plays an important role in CNS acid-base homeostasis, yet the mechanisms underlying its control remain uncertain. The role of net flux of chloride will be evaluated by studying the CSF electrolyte and acid-base composition following administration of chloride transport inhibitors and/or acid-base disturbances in anesthetized dogs. Quantitative estimates of the individual unidirectional fluxes of radiolabelled chloride between blood, CSF, brain ECF in anesthetized dogs will be made. The use of a short half-lived isotope, will allow multiple studies to be performed in a given animal, permitting each animal to serve as its own control. By studying the effects of chloride transport inhibitors and acid-base status, a good understanding of the role of chloride movements in CNS acid-base regulation will be gained which will have direct relevance to central drive to respiration in normal and disease states.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL029620-05
Application #
3340748
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1983-01-01
Project End
1988-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Burton, M D; Kazemi, H (2000) Neurotransmitters in central respiratory control. Respir Physiol 122:111-21
Ang, R C; Hoop, B; Kazemi, H (1992) Brain glutamate metabolism during metabolic alkalosis and acidosis. J Appl Physiol 73:2552-8
Kazemi, H; Hoop, B (1991) Glutamic acid and gamma-aminobutyric acid neurotransmitters in central control of breathing. J Appl Physiol 70:1-7
Hoop, B; Masjedi, M R; Shih, V E et al. (1990) Brain glutamate metabolism during hypoxia and peripheral chemodenervation. J Appl Physiol 69:147-54
Burton, M D; Johnson, D C; Kazemi, H (1990) Adrenergic and cholinergic interaction in central ventilatory control. J Appl Physiol 68:2092-9
Johnson, D C; Nishimura, M; Okunieff, P et al. (1989) Effects of hypothermia on rat brain pHi and phosphate metabolite regulation by 31P-NMR. J Appl Physiol 67:2527-34
Nishimura, M; Johnson, D C; Hitzig, B M et al. (1989) Effects of hypercapnia on brain pHi and phosphate metabolite regulation by 31P-NMR. J Appl Physiol 66:2181-8
Burton, M D; Johnson, D C; Kazemi, H (1989) CSF acidosis augments ventilation through cholinergic mechanisms. J Appl Physiol 66:2565-72
Nishimura, M; Johnson, D C; Kazemi, H (1988) Effects of inhibitors on chloride outflux from cerebrospinal fluid. J Appl Physiol 64:2183-9
Hoop, B; Systrom, D M; Shih, V E et al. (1988) Central respiratory effects of glutamine synthesis inhibition in dogs. J Appl Physiol 65:1099-109

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