Gene/Protein Disease Symptom Drug Enzyme Compound
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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

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

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

L-Glutamate was microinjected into the nucleus tractus solitarii (NTS) in anesthetized (chloralose and urethane), paralyzed and artificially ventilated rats, and spinal cord blood flow (SCBF) was determined using a combination of labeled microspheres. Unilateral chemical stimulation of the NTS (n = 13) significantly decreased SCBF in the cervical cord from 43 +/- 6 (mean +/- SEM) to 28 +/- 4 (P < 0.05), in the thoracic cord from 35 +/- 3 to 24 +/- 4 (P < 0.01), and in the lumbar cord from 49 +/- 3 to 40 +/- 3 ml min-1 (100 g)-1 (P < 0.05). The decrease in SCBF was not due to the decrease in arterial blood pressure (ABP) because the SCBF during the chemical stimulation of the NTS was significantly smaller (P < 0.05) than the SCBF during controlled hemorrhagic hypotension (n = 11). Chemical stimulation of the NTS did not affect the reactivity of the spinal cord vessels to hypercapnia (n = 5). Microinjection of the vehicle solution into the NTS had no effects on spinal cord circulation (n = 9). These results suggest that the cell bodies within the NTS may play a role in the control of spinal cord circulation.
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PMID:Chemical stimulation of the nucleus tractus solitarii decreases spinal cord blood flow in anesthetized rats. 774 99

Cerebral microvascular endothelial cells (CMVECs) have recently been implicated as targets of excitotoxic injury by l-glutamate (l-glut) or N-methyl-d-aspartate (NMDA) in vitro. However, high levels of l-glut do not compromise the function of the blood-brain barrier in vivo. We sought to determine whether primary cultures of rat and piglet CMVECs or cerebral microvascular pericytes (CMVPCs) are indeed sensitive to l-glut or NMDA. Viability was unaffected by 8-h exposure to 1-10 mM l-glut or NMDA in CMVECs or CMVPCs isolated from both species. Furthermore, neither 1 mM l-glut nor NMDA augmented cell death induced by 12-h oxygen-glucose deprivation in rat CMVECs or by 8-h medium withdrawal in CMVPCs. Additionally, transendothelial electrical resistance of rat CMVEC-astrocyte cocultures or piglet CMVEC cultures were not compromised by up to 24-h exposure to 1 mM l-glut or NMDA. The Ca(2+) ionophore calcimycin (5 microM), but not l-glut (1 mM), increased intracellular Ca(2+) levels in rat CMVECs and CMVPCs assessed with fluo-4 AM fluorescence and confocal microscopy. CMVEC-dependent pial arteriolar vasodilation to hypercapnia and bradykinin was unaffected by intracarotid infusion of l-glut in anesthetized piglets by closed cranial window/intravital microscopy. We conclude that cerebral microvascular cells are insensitive and resistant to glutamatergic stimuli in accordance with their in vivo role as regulators of potentially neurotoxic amino acids across the blood-brain barrier.
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PMID:Cerebromicrovascular endothelial cells are resistant to L-glutamate. 1866 11

Mutational changes in p53 correlate well with tumorigenesis. Remarkably, however, relatively little is known about the role that p53 variations may play in environmental adaptation. Here we report that codon asparagine-104 (104N) and glutamic acid-104 (104E), respectively, of the p53 gene in the wild zokor (Myospalax baileyi) and root vole (Microtus oeconomus) are adaptively variable, meeting the environmental stresses of the Tibetan plateau. They differ from serine-104 (104S) seen in other rodents, including the lowland subterranean zokor Myospalax cansus, and from serine 106 (106S) in humans. Based on site-directed mutational analysis in human cell lines, the codon 104N variation in M. baileyi is responsible for the adaptive balance of the transactivation of apoptotic genes under hypoxia, cold, and acidic stresses. The 104E p53 variant in Microtus oeconomus suppresses apoptotic gene transactivation and cell apoptosis. Neither 104N nor 104E affects the cell-cycle genes. We propose that these variations in p53 codon 104 are an outcome of environmental adaptation and evolutionary selection that enhance cellular strategies for surviving the environmental stresses of hypoxia and cold (in M. baileyi and M. oeconomus) and hypercapnia (in M. baileyi) in the stressful environments of the Qinghai-Tibet plateau.
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PMID:Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau. 2506 40