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

The metabolic effects of 60-min exposure to 250-2000 mg gamma-hydroxybutyrate (GHB) per kilogram or 150-1200 mg gamma-butyrolactone (GBL) per kilogram were studied in rats by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic-Krebs' cycle metabolites. A general pattern of increased glycogen and glucose with decreased pyruvate, lactate, alpha-ketoglutarate, and malate was observed. This pattern in association with unchanged adenylates and decreased energy phosphate utilization was consistent with a metabolic adaptation to a state of cerebral depression. The major qualitative difference between the two drugs was that higher doses of GBL were associated with additional decreases of citrate and glutamate. Since these doses of GBL were also associated with acute increases of arterial CO2 tension, it is proposed that these differences were secondary to hypercapnia and not due to a distinctive primary action of GBL. Derivation of the cytoplasmic NAD(P)H:NAD(P)+ ratios indicated that GHB and GBL were not associated with consistent alterations of the cytoplasmic redox state.
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PMID:A comparison of the effects of gamma-hydroxybutyrate and gamma-butyrolactone on cerebral carbohydrate metabolism. 4 Jun 77

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

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

Results from several studies suggest that the ventrolateral medulla (VLM) is involved in modulating the respiratory response to central and/or peripheral chemoreceptor stimulation. Furthermore, the excitatory amino acid (EAA) glutamate has been shown to have marked effects on respiration when administered to VLM sites. The purpose of this study was to determine if an excitatory amino acid mechanism in the VLM modulates the respiratory responses to hypoxia or hypercapnia in anesthetized rats. Exposure to hypoxic or hypercapnic gas under control conditions elicited increases in respiratory activity (diaphragmatic EMG activity and breathing frequency). Bilateral injection of kynurenic acid (KYN), an EAA antagonist, into rostral VLM sites evoked significant increases in breathing frequency; injections more caudal in the VLM typically caused apnea. Significantly larger increases in respiratory output were elicited by both hypoxia and hypercapnia after rostral VLM microinjections of KYN. The accentuated responses returned to control levels after a recovery of approximately 100 min. Microinjection of xanthurenic acid (XAN), an inactive analog of kynurenic acid, into the VLM prior to KYN had only slight effects on resting respiratory activity and no effects on the responses to hypoxia or hypercapnia. These results suggest two separate VLM sites which modulate respiration by EAA mechanisms. A more rostral site tonically inhibits respiratory activity and the respiratory responses to chemoreceptor stimulation and more caudal VLM sites may be required for the maintenance of respiratory activity.
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PMID:Modulation of respiratory reflexes by an excitatory amino acid mechanism in the ventrolateral medulla. 165

We review recent cross-disciplinary experimental and theoretical investigations on metabolism of the amino acid neurotransmitters glutamic acid and gamma-aminobutyric acid (GABA) in the brain during hypoxia and hypercapnia and their possible role in central control of breathing. The roles of classical modifiers of central chemical drive to breathing (H+ and cholinergic mechanisms) are summarized. A brief perspective on the current widespread interest in GABA and glutamate in central control is given. The basic biochemistry of these amino acids and their roles in ammonia and bicarbonate metabolism are discussed. This review further addresses recent work on central respiratory effects of inhibitory GABA and excitatory glutamate. Current understanding of the sites and mechanisms of action of these amino acids on or near the ventral surface of the medulla is reviewed. We focus particularly on tracer kinetic investigations of glutamatergic and GABAergic mechanisms in hypoxia and hypercapnia and their possible role in the ventilatory response to hypoxia. We conclude with some speculative remarks on the critical importance of these investigations and suggest specific directions of research in central mechanisms of respiratory control.
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PMID:Glutamic acid and gamma-aminobutyric acid neurotransmitters in central control of breathing. 167 87

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

Previous studies have demonstrated that electrolytic lesions placed in the midline at the pontomedullary junction result in increased respiratory frequency. The increase in frequency is greater during hypercapnia. The present study sought to determine whether the effects of the lesions were mediated, at least in part, by destruction of neurons. Alternatively, the lesions may have interrupted fiber tracts. Both destruction by kainic acid and inhibition by selective cooling of neurons on the midline at the pontomedullary junction in decerebrate, vagotomized, paralyzed and artificially ventilated cats produced results similar to those engendered by the lesions; i.e., an increased respiratory frequency. Microinjections of glutamate produced a slowing of respiration. In additional cats, extracellular single unit recordings were obtained from 48 neurons located in the medial areas (0-1 mm lateral to midline) at the pontomedullary junction. Of these, 41 neurons were tonically active and 38 were judged to be respiratory-modulated by both the F-test and the Friedman test. The activity of these neurons was sensitive to changes in CO2. Therefore, neurons located at the pontomedullary junction may play a primary role in the integration of central chemoreceptor afferent stimuli.
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PMID:Function in ventilatory control of respiratory neurons at the pontomedullary junction. 404 67

The effects of hyperlactatemia on cerebral glucose metabolism of normoglycemic 20-day-old rats were studied in animals breathing air or 20% CO2:21% O2:59% N2. Sodium lactate or sodium bicarbonate were given intraperitoneally, together with a mixture of [3H]deoxyglucose and [2-14C]glucose. Animals were sacrificed in a freeze-blowing apparatus at intervals of 2-15 min after injection. Blood lactate levels in the lactate-injected rats were 4-6 mM. Hyperlactatemia caused a gradual decline in the brain rate of glucose utilization in air-breathing animals to 50-70% of control rates. Results with both tracers were similar. Concentrations of Krebs cycle intermediates and glutamate did not decrease. These findings indicate that lactate can partially replace glucose as an oxidative fuel for developing rat brain. Hypercapnia depressed the rate of glucose utilization by developing brain and rates were 30-40% lower still in lactate-injected hypercapnic rats. Decreases in levels of Krebs cycle intermediates and glutamate were similar in both groups. Thus, lactate and CO2 are additive in their depressant effects on brain glucose utilization. The observation that lactate did not prevent the decreases in Krebs cycle intermediates and glutamate caused by hypercapnic acidosis suggests an inhibition of flux through pyruvate dehydrogenase during hypercapnia. The data from this study, coupled with data on lactate transport across the blood-brain barrier, indicate that the direction of movement of lactate and its rate of utilization by developing brain are functions of its concentration on blood relative to brain. Physiological and pathological conditions which elevate blood lactate levels above those in brain will, then, have a sparing effect upon brain glucose utilization.
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PMID:Effects of lactate on glucose metabolism of developing rat brain. 632 76

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

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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