Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085383 (hypocapnia)
 1,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that severe insulin-induced hypoglycemia would depress cerebrovascular reactivity to CO2 via a mechanism that could be prevented by administration of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in infant piglets. Cerebral blood flow (CBF) was measured (microspheres) in 2- to 3-wk-old pentobarbital-anesthetized piglets during hypocapnia, normocapnia, and hypercapnia. Repeat CBF measurements were made either 1 (n = 5) or 2 h (n = 6) after insulin (200 U/kg iv) to elicit the time course of altered reactivity to CO2. Repeat CBF measurements were made in a third group (n = 5) 2 h after treatment with insulin and MK-801 (1.5 mg/kg iv bolus, 0.15 mg.kg-1.h-1 iv infusion) to determine whether any alteration in reactivity to CO2 was due to a mechanism involving the NMDA receptor. Cerebrovascular resistance and cerebral O2 consumption (CMRO2) were calculated with each measurement of CBF. Cerebrovascular response to CO2 (change in cerebrovascular resistance/change in arterial CO2 tension) was ablated in the group of piglets exposed to 1 or 2 h of hypoglycemia (preinsulin 1-h group, 0.038 +/- 0.007; preinsulin 2-h group, 0.023 +/- 0.004 mmHg.ml-1.min.100 g.mmHg CO2(-1)). Treatment with MK-801 did not alter normoglycemic CO2 reactivity (preinsulin, 0.032 +/- 0.005 mmHg.ml-1.min.100 g.mmHg CO2(-1)) and did not prevent ablation of cerebrovascular CO2 reactivity during hypoglycemia. CMRO2 was not affected by hypoglycemia in any group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:MK-801 does not prevent impaired cerebrovascular reactivity to CO2 during hypoglycemia in piglets. 832 42

The present study tests the hypothesis that cerebral ischemia induced by severe hypocapnia modifies the N-methyl-D-aspartate (NMDA) receptor/ion channel complex in the cerebral cortical cell membranes of newborn piglets. Studies were performed in six newborn piglets subjected to ischemic hypoxia induced by hyperventilation (PaCO2, 9-11 mmHg) for 1 h. Comparisons were made to a normoxic group on room air (n = 6). Following hyperventilation, phosphocreatine decreased 80%, but ATP remained unchanged. NMDA receptor activation was determined by measuring [3H]MK-801 binding at concentrations varying from 2.5 to 50 nM. Following hyperventilation, Bmax decreased 52% to 0.50 +/- 0.04 pmol/mg protein (P = 0.001); however, the Kd value was unchanged at 7.45 +/- 0.79 nM. Spermine and magnesium dependent activation of the NMDA receptor was determined in the hyperventilated and control groups. With spermine concentrations increasing from 2.5 to 50 microM the maximal spermine dependent activation in the normoxic group was 13.7 +/- 7.93% which occurred at a concentration of 3.75 +/- 1.37 microM. In the hyperventilated group maximal activation was 32.4 +/- 23.5% (P = 0.095) at 4.58 +/- 2.46 microM (P = ns). With magnesium concentrations increasing from 2.5 to 100 microM the maximal magnesium dependent activation in the normoxic group was 17.0 +/- 13.6% which occurred at a concentration of 22.5 +/- 6.12 microM. In the hyperventilated group maximal activation was 26.3 +/- 14.9% (P = ns) at 4.58 +/- 2.92 microM (P < 0.0001). These data show that with less severe tissue hypoxia, as evidenced by conservation of ATP, there is less modification of the NMDA receptors. Ischemia induced by hyperventilation leads to an increase in spermine activation of the NMDA receptor, and the NMDA receptor is much more sensitive to magnesium as evidenced by the maximal activation occurring at a significantly lower magnesium concentration. Ischemia induced by hyperventilation modifies the spermine, magnesium, and MK-801 binding sites of the NMDA receptor and may result in increased NMDA receptor mediated neurotoxicity in the newborn brain.
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PMID:Modification of the N-methyl-D-aspartate (NMDA) receptor in the brain of newborn piglets following hyperventilation induced ischemia. 893 73