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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the role of carbonic anhydrase in the CSF [HCO3] increase in respiratory acidosis and its effect on brain ammonia, anesthetized rats were subjected to hypercapnia (7% CO2) for 2 hours. The animals received periodic intraventricular injections of either 'mock' CSF or 'mock' CSF and acetazolamide for 45 minutes prior and during hypercapnia when: (a) plasma [HCO3-] was allowed to increase normally and (2) plasma [HCO3] increase was prevented by i.v. HC1 infusion, CSF [HCO3] increased 8.5 mM/L after 2 hours of hypercapnia (delta PCO2 40) in the rats with intraventricular 'mock' CSF injections, and only 6 mM/L in the animals with acetazolamide injections. CSF [HCO3-] increased 7 mM/L during hypercapnia and HCl infusion with intraventricular 'mock' CSF injections, but only 2 mM/L with acetazolamide injections. Changes in total brain CO2 (increase) and brain glutamic acid (decrease) in hypercapnia were not affected by intraventricular acetazolamide and i.v. HCl. The increase of brain NH4+ and glutamine in hypercapnia was reduced in these conditions. It is concluded that there are at least two sources for the CSF [HCO3-] increase in hypercapnia; one formed in the CNS and dependent on carbonic anhydrase, and the other derived from plasma [HCO3-] increase.
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PMID:The CSF HCO3 increase in hypercapnia relationshp to HCO3, glutamate, glutamine and NH3 in brain. 1 66

In order to study the influence of hypercapnia on the content of glutamate and glutamine in the developing brain, pregnant rats and their offspring were kept in CO2 rich (6-10%) atmosphere and the litters were killed at different ages between 4 and 28 days. In the hypercapnic rats the content of both amino acids in the brain increases with age with almost the same time course as in normocapnic rats. At any age the glutamate content is lower in the hypercapnic animals than in control rats, whereas the glutamine content, beyond the first 8 days of life is increased. Both effects are rapidly reversible on return to air breathing. Although the glutamate-glutamine system is in full development, the influence of hypercapnia can be compared to that observed in adult rats. Hypercapnia did not change the glutaminase and the glutamine synthetase activity of the brain.
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PMID:Glutamate and glutamine in the brain of the neonatal rat during hypercapnia. 7 Oct 88

Glutamic, aspartic, and gamma-aminobutyric acid (GABA), glutamine, and ammonium were measured in the brains of unanesthetized normocapnic and hypercapnic (10% CO2; 5 min to 3 wk) rats. Hypercapnia increased glutamine and GABA and decreased glutamic and aspartic acids. Changes occurred within 1 h and were maintained during the observation period of 3 wk. On return to normocapnia amino acid concentrations were almost normal after 1 h. Based on the time course it is concluded that intracerebral hypercapnia is more likely the stimulus for change than acidosis. Ammonium content was unchanged for at least 1 h after the onset of hypercapnia but increased thereafter. Experiments in which glutamine synthesis by brain was impeded by inhibiting the enzyme glutamine synthetase favor the hypothesis that the rise of ammonium content in hypercapnia is initially not seen because of increased glutamine synthesis. The changes observed may have a role in metabolic pH homeostasis of brain tissue and may also be relevant to the modified brain excitability in hypercapnia.
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PMID:Selected brain amino acids and ammonium during chronic hypercapnia in conscious rats. 63 72

Experiments in rats during acute and prolonged periods of hypercapnia show important changes in the glutamate and glutamine content of the brain. Compartmentation studies using labelled glutamate intracisternally injected show an increased turnover of the small glutamate compartment. The possible pathophysiological significance of these observations is discussed.
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PMID:Brain organic acids during hypercapnia. 101 84

Hyperammonemia increases brain glutamine levels, causes astrocytic swelling, and depresses cerebral blood flow (CBF) responsivity to CO2. Methionine sulfoximine (MSO) inhibition of glutamine synthetase activity, known to be enriched in astrocytes, prevents ammonia-induced increases in brain glutamine and water content. We tested the hypothesis that inhibition of glutamine accumulation restores CBF responsivity to CO2 during acute hyperammonemia. Pentobarbital-anesthetized rats treated with either vehicle or MSO (150 mg/kg i.p.) received a 6-hour intravenous infusion of either sodium or ammonium acetate. With subsequent induction of hypercapnia, CBF increased from 113 +/- 14 (mean +/- SEM) to 194 +/- 9 ml/min per 100 g in control rats but was unchanged from 107 +/- 13 to 79 +/- 10 ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic rats restored the CBF response to hypercapnia (from 73 +/- 8 to 141 +/- 14 ml/min per 100 g). With induction of hypocapnia, CBF decreased from 114 +/- 11 to 88 +/- 11 ml/min per 100 g in control rats but increased from 112 +/- 13 to 142 +/- 19 ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic rats did not fully restore the response to hypocapnia but prevented the paradoxical increase in CBF (from 80 +/- 8 to 80 +/- 8 ml/min per 100 g). In control rats, MSO did not affect CO2 responsivity. Treatment with MSO prevented ammonia-induced increases in intracranial pressure. Hyposmotic-induced increases in brain water content and intracranial pressure attenuated the CBF response to hypercapnia but, unlike hyperammonemia, did not attenuate the response to hypocapnia. In contrast to hypercapnia, vasodilation in response to arterial hypotension was intact in hyperammonemic rats. We conclude that the grossly abnormal CBF responsivity to CO2 alterations during hyperammonemia is linked to glutamine accumulation rather than ammonia per se. Cerebral edema secondary to glutamine accumulation may contribute in part to abnormal CBF responses, although other aspects of astrocyte dysfunction are likely to be important.
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PMID:Restoration of cerebrovascular CO2 responsivity by glutamine synthesis inhibition in hyperammonemic rats. 139 82

Resting level of ventilation is affected by change in extracellular fluid hydrogen ion concentration [H+] in the central nervous system (CNS) and by certain amino acid neurotransmitters within or near the medulla oblongata. Hypercapnia alters both cerebrospinal fluid (CSF) [H+] and CSF ammonia metabolized to glutamine, a precursor of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Therefore, the effect of 1 to 2 h of hypercapnia on cerebral cortical and medullary contents of selected amino acids and bicarbonate (HCO-3) fixation rates was studied in anesthetized mongrel dogs using 11C-labeled HCO-3. Medullary taurine, glycine, alanine, and glutamate concentrations were not significantly altered by hypercapnia, but mean medullary glutamine and GABA concentrations both increased significantly (p less than 0.05), with a high correlation (r = 0.82, n = 8) between individual values. Medullary GABA and glutamine increased linearly with CSF [H+]. The rate of CNS HCO-3 fixation into CSF glutamine was negligibly small and decreased during hypercapnia, compared with the rate of medullary tissue HCO-3 fixation, which increased linearly with CSF [H+]. These observations show that there is a significant interrelationship between medullary metabolism of GABA, glutamine, bicarbonate, and CNS hydrogen ion regulation during hypercapnia.
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PMID:Relationship between central nervous system hydrogen ion regulation and amino acid metabolism in hypercapnia, II. 286 18

The renal medulla can play an important role in acid excretion by modulating both hydrogen ion secretion in the medullary collecting duct and the medullary PNH3. The purpose of these experiments was to characterize the intrarenal events associated with ammonium excretion in acute acidosis. Cortical events were monitored in two ways: first, the rates of glutamine extraction and ammoniagenesis were assessed by measuring arteriovenous differences and the rate of renal blood flow; second, the biochemical response of the ammoniagenesis pathway was examined by measuring glutamate and 2-oxoglutarate, key renal cortical metabolites in this pathway. There were no significant differences noted in any of these cortical parameters between acute respiratory and metabolic acidosis. Despite a comparable twofold rise in ammonium excretion in both cases, the urine pH, PNH3, and the urine minus blood PCO2 difference (U-B PCO2) were lower during acute hypercapnia. In these experiments, the urine PCO2 was 34 mmHg (1 mmHg = 133.322 Pa) lower than that of the blood during acute respiratory acidosis while the U-B PCO2 was 5 +/- 3 mmHg in acute metabolic acidosis. Thus there were significant differences in medullary events during these two conditions. Although the urine pH is critical in determining ammonium excretion in certain circumstances, these results suggest that regional variations in the medullary PNH3 can modify this relationship.
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PMID:Importance of medullary events in ammonium excretion: studies in acute respiratory and acute metabolic acidosis. 640 34

Animal studies and theoretical considerations have suggested that in hypercapnic respiratory failure there is interconversion of glutamic acid to glutamine within the brain, perhaps as part of a local buffering mechanism to minimize hypercapnia-induced cerebral acidosis. Detection of transcerebral arteriovenous differences, positive for glutamic acid and negative for glutamine, would lend support to this hypothesis. We measured arterial and internal jugular venous levels of twenty-three aminoacids in four patients with hypercapnic respiratory failure and in four suitable controls. In patients, arterial as well as venous glutamine levels were elevated proportionally, and there was no demonstrable A-V difference across the brain; arterial and venous glutamic acid levels were the same as controls. All other aminoacid levels, arterial and venous, were normal. These findings confirm the previous observations that in hypercapnic respiratory failure glutamine metabolism is altered, but provide no support for the proposed glutamic acid-glutamine interconversions within the brain.
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PMID:Plasma aminoacid levels across the brain in patients with respiratory failure. 640 28

Resting level of ventilation is affected by change in hydrogen ion [H+] and by certain amino acid neurotransmitters in the brain and cerebral fluids. Hypercapnia alters both [H+] and amino acid content. Therefore, the effect of 90 min of hypercapnia on blood and cerebrospinal fluid (CSF) contents of selected amino acids and ammonia was studied in anesthetized mongrel dogs using 13N-labeled ammonia. Metabolic turnover of CSF ammonia was not significantly altered by hypercapnia, but CSF equilibrium concentration of metabolized ammonia, i.e., glutamine, a precursor of the neurotransmitters glutamic acid and gamma amino butyric acid, varied linearly with CSF bicarbonate and hydrogen ion concentration. The percentage of CSF glutamine derived from tracer-labeled ammonia metabolized in the central nervous system (CNS) rose from 30% at normocapnia to 60% after 90 min of hypercapnia, whereas at the same time, the CSF transfer rate of glutamine increased by a factor of 2. These observations show that there is a significant correlation between CNS transfer of glutamine and CNS hydrogen ion regulation during hypercapnia.
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PMID:Relationship between central nervous system hydrogen ion regulation and amino acid metabolism in hypercapnia. 687 69

Studies were performed to determine whether ammoniagenesis could adapt instantaneously to acidosis in the dog kidney. Following acute respiratory acidosis, renal glutamine extraction rose acutely in dogs with stable renal blood flow but did not change when the renal blood flow fell by more than 25%. Acute hypercapnia immediately increased renal ammonia production in both groups of dogs. The rate of both glutamine extraction and ammonia production in acutely hypercapnic dogs without hemodynamic changes was comparable to the rates observed in dogs with chronic metabolic acidosis. Furthermore, the renal metabolite profile observed in acute hypercapnia was similar to the pattern described in chronic metabolic acidosis, i.e., a marked fall in renal glutamate and alpha-ketoglutarate concentrations and a fivefold increase in malate and oxaloacetate concentrations. In the liver and muscle, acute hypercapnia induced no significant change in glutamine concentration but glutamate and alpha-ketoglutarate concentrations decreased. Our findings demonstrate that the dog kidney can adapt immediately to acidosis but that hemodynamic change may mask this adaptation.
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PMID:Immediate adaptation of the dog kidney to acute hypercapnia. 711 53


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