Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activity of glutaminase (both phosphate-dependent and phosphate-independent forms of the enzyme) as well as glutamate decarboxylase activity were studied in hyperoxia (6 ati) and under conditions of protection by means of arginine from the effect of hyperoxia. In hyperoxia activity of phosphate-dependent and phosphate-independent forms of glutaminase was decreased by 45% and 51%, respectively. At the same time, glutamate decarboxylase activity was decreased by 32%. Arginine showed a protective effect, delaying the time of oxygen convulsions onset by 2.5-fold. The low activities of glutaminases were maintained but the glutamate decarboxylase activity was increased and even exceeded the control level by 29%. A mechanism of the protective effect of arginine is discussed.
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PMID:[Protective effect of arginine in hyperoxia. Activity of cerebral glutaminase and glutamate decarboxylase]. 66 82

Water-insoluble proteins of rat brain were studied as affected by hyperbaric oxygenation (oxygen pressure 6 at.ga. convulsion state). Solubilization of proteins under effect of hyperoxia and triton X-100 increases by 32-81%. Changes in the amino acidic composition of proteins extracted by 0.5% triton X-100 are characterized by an increase in the amount of aspartic acid, cystin, leucine and isoleucine and by a decrease in the amount of histidine, arginine and methionine. Electrophoresis in 7.5% polyacrylamide gel of proteins in the 0.5% triton X-100 extract showed changes in the number and mobility of protein bands.
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PMID:[Effect of hyperoxia on water-insoluble proteins of the brain]. 68 68

Experiments were designed to investigate the role of oxygen tension on modulation of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) synthase activity. EDRF/NO synthase from bovine cerebellum was confirmed to have cofactor and kinetic characteristics similar to that reported in endothelium and other tissues. The effect of oxygen tension on EDRF/NO synthase activity as assessed by L-[3H]citrulline production was investigated. Hypoxia markedly inhibited EDRF/NO synthase activity whereas hyperoxia increased the initial rate of enzyme activity. The inhibition of EDRF/NO synthase activity by hypoxia was reversed by normoxia as well as by hyperoxia. The Km values for L-arginine in hyperoxia, normoxia and hypoxia were 7 +/- 0.7, 4.8 +/- 0.4 and 7 +/- 1.3 microM whereas the Vmax values were 94 +/- 8, 66 +/- 7, and 32 +/- 2 pmol/min/mg of protein, respectively. The effect of oxygen tension on EDRF/NO synthase activity as determined by L-[3H]citrulline production was correlated with EDRF/NO production using a bioassay in which an EDRF/NO synthase preparation was incubated in wells of cultured vascular smooth muscle and cyclic GMP production was measured. Hypoxia almost inhibited the production of cyclic GMP completely, which was comparable to its inhibition of L-[3H]citrulline production. Hyperoxia, however, showed partial inhibition of cyclic GMP accumulation with no significant effect on L-[3H]citrulline production. This cyclic GMP inhibition by hyperoxia was reversed partially by superoxide dismutase. We conclude that hypoxia inhibits EDRF/NO synthase activity primarily through depletion of oxygen, one of the substrates for the enzyme. In hyperoxia, the initial rate of EDRF/NO synthase activity (Vmax) is significantly enhanced with no significant change in enzyme activity at longer time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of endothelium-derived relaxing factor/nitric oxide synthase from bovine cerebellum and mechanism of modulation by high and low oxygen tensions. 171 81

We have investigated the influence of endogenous nitric oxide (NO) on the vascular resistance of isolated rat lungs by inhibiting its synthesis with the false substrate N-monomethyl-L-arginine (L-NMMA). When perfused with blood at constant flow the addition of L-NMMA (10(-3) M) did not affect pulmonary arterial pressure in hyperoxia but did increase the response to hypoxia (PO2 25-35 mmHg) by 2.5 +/- 0.2 fold (mean +/- S.E.M.). The effect of L-NMMA was reversed by 3 x 10(-3) M-L-arginine, the true substrate for NO synthesis. Thus NO is an important pulmonary vasodilator but hypoxic vasoconstriction does not result from a reduction of its background release.
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PMID:Inhibition of nitric oxide synthesis potentiates hypoxic vasoconstriction in isolated rat lungs. 234 Jan 64

Alveolar fibrin deposition commonly occurs in the lungs of patients with the adult respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) from patients with ARDS, control patients with interstitial lung disease (ILD), congestive heart failure, or exposure to hyperoxia, and normal healthy subjects was studied to determine whether local alterations in procoagulant activity favor alveolar fibrin deposition in the lungs in ARDS. Procoagulant activity capable of shortening the recalcification time of plasma deficient in either factor VII or factor VIII was observed in unconcentrated BAL of all patients, but was significantly greater in BAL from patients with ARDS when compared with that of control subjects (p less than 0.001). Unconcentrated BAL from patients with ARDS shortened the recalcification time of plasma deficient in factor X, but no functional thrombin was detectable. BAL procoagulant from patients with ARDS was inhibited by concanavalin A, an inhibitor of tissue factor. The hydrolysis of purified human factor X by BAL from the ARDS and other patient groups was determined by measuring the amidolytic activity of generated factor Xa on its N-benzoyl-L-isoleucyl-L-glutamyl-glycyl-L-arginine-p-nitroanilide substrate. The procoagulant activity of BAL was associated with the development of amidolytic activity, indicating activation of factor X. BAL from patients with ARDS contained more factor X activating activity than did BAL from control groups (p less than 0.001). This activity was calcium dependent and was maximal at 1 mM ionized calcium. The BAL factor X activating activity was most active at neutral pH and was sedimented by ultracentrifugation at 100,000 x g.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome. Contribution of tissue factor associated with factor VII. 368 50

The effect of protective concentrations of arginine on the arginase activity and the content of rat brain and liver spermidine and spermine was studied under hyperoxia (6 atmospheres). Intraperitoneal injection of arginine to intact animals increases the arginase activity and the brain content of spermidine and spermine by 15, 19 and 25%, respectively. The liver arginase activity rises by 55%, while the level of the polyamines remains almost unchanged. Arginine injection before hyperoxic exposure prevents the significant lowering of the arginase activity and polyamine content seen in the unprotected animals. The relationship between the arginase activity and the polyamine level in the brain and liver is discussed with emphasis on arginine efficacy as protective agent in hyperoxia.
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PMID:[Cerebral and hepatic arginase and polyamines in the mechanisms of the protective effect of arginine in hyperoxia]. 726 Mar 63

L-Arginine is the substrate for synthesis of nitric oxide (NO.) by NO synthase which physiologically produces vasodilation. The reaction of NO. or its metabolites with O2 or its metabolites, however, can produce toxic reactive species which may cause cellular injury. We hypothesized that excessive NO. production in isolated perfused rabbit lungs at elevated PO2 could support the production of toxic nitrogen metabolites. In isolated perfused rabbit lungs ventilated with 95% O2, 1.0 mM L-arginine caused significant pulmonary hypertension and edema. These effects of L-arginine were attenuated by the NO. synthase inhibitor, L-NAME (0.5 mM), not affected by SOD pretreatment (100 u/ml) and reversed by pretreatment with catalase (200 u/ml), suggesting a mechanism involving H2O2. This mechanism was supported by producing L-arginine mediated injury in normoxic lungs in the presence of a H2O2 generating system. This injury also was attenuated by L-NAME. On the basis of these results, we conclude that H2O2 interacts with NO. or one of its oxidized metabolites to contribute to acute lung injury during hyperoxia. Such a mechanism may involve peroxynitrite anion, although direct proof of its formation is lacking under these conditions.
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PMID:L-arginine enhances injury in the isolated rabbit lung during hyperoxia. 754 44

To determine whether hyperoxia increases the production of endothelium-derived relaxing factor, we studied the effect of oxygen on pulmonary vascular ring tension and regional lung perfusion. In vitro, hyperoxia stimulated endothelium-independent constriction of neonatal porcine pulmonary arterial rings. In vessels with intact endothelium, hyperoxia stimulated a concomitant increase in the production of endothelium-derived relaxing factor. In sedated neonatal pigs, colored microspheres were used to evaluate relative lung perfusion when two lung regions were independently ventilated with room air, and subsequently, when one lung region was ventilated with 100% oxygen. The proportion of flow to the hyperoxic lung region was not significantly increased until the production of endothelium-derived relaxing factor was inhibited by NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester. Thus, hyperoxia stimulated opposing effects on the tension of isolated vascular rings. One mechanism of oxygen-mediated relaxation results from an increase in the production of endothelium-derived relaxing factor. However, in vivo, alveolar hyperoxia may stimulate an acute pulmonary vasodilatory response which is not mediated by endothelium-derived relaxing factor.
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PMID:Endothelium-dependent relaxation and the acute pulmonary vascular response to alveolar hyperoxia in neonatal pigs. 837 12

CNS oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for depletion of the brain GABA pool has been proposed, although recent data have implicated production of reactive O2 species, e.g. H2O2, in this process. We hypothesized that the production of H2O2 and NH3 produced by monoamine oxidase (MAO) would lead to depletion of GABA and production of nitric oxide (NO.) respectively, and thereby enhance CNS O2 toxicity. In this study, rats treated with an MAO inhibitor (pargyline) or a nitric oxide synthase inhibitor (LNNA) were protected against O2-induced convulsions. Selected cerebral amino acids including arginine were measured in control and O2 treated rats (6 ATA, 20 min) with or without drug pretreatment. After O2 exposure, the cerebral pools of glutamate, aspartate, and GABA decreased significantly while glutamine content increased relative to control (P < 0.05). After treatment with either enzyme inhibitor, glutamine, glutamate and aspartate concentrations were maintained near control levels. Remarkably, GABA depletion by O2 was not prevented despite protection from seizures by both pargyline and LNNA. The NO. precursor, arginine, was increased significantly in the brain by toxic O2 exposure, but both pargyline and LNNA inhibited this effect. Simultaneous norepinephrine measurements indicated that its storage substantially decreased during hyperoxia (P < 0.05), but this effect too was blocked by either pargyline or LNNA. These data indicate that protection against O2 by these inhibitors is not related to preservation of the GABA pool. More importantly, O2 dependent norepinephrine metabolism and NO. synthesis appear to be interactive during CNS O2 toxicity.
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PMID:Cerebral amino acid, norepinephrine and nitric oxide metabolism in CNS oxygen toxicity. 846 4

Supplemental oxygen and alkalosis are the most effective treatments used to lower pulmonary arterial pressure in children with pulmonary hypertensive disorders. However, their mechanisms of action are unknown. Endothelium-derived nitric oxide (EDNO) is an important mediator of pulmonary vascular tone and produces potent pulmonary vasodilation during pulmonary hypertension. In vitro evidence suggests that EDNO may mediate the vasodilating effects of oxygen. To investigate whether EDNO synthesis mediates the pulmonary vasodilation produced by hyperoxia [normocarbic ventilation with 100% oxygen, arterial oxygen tension > 450 torr (60 kPa)] or alkalosis (hyperventilation with 21% oxygen, pH > 7.55) in vivo, eight intact newborn lambs were studied during similar degrees of pulmonary hypertension induced either by the infusion of U46619 (a thromboxane A2 mimic) or N omega-nitro-L-arginine (an inhibitor of EDNO synthesis). The lambs were sedated, paralyzed, and mechanically ventilated. Meclofenamic acid was infused to inhibit prostaglandin synthesis. During pulmonary hypertension induced by U46619, pulmonary arterial pressure and pulmonary vascular resistance were significantly decreased by acetylcholine (an EDNO-dependent vasodilator) (23.1 +/- 3.4% and 43.3 +/- 14.5%, respectively), hyperoxia (26.8 +/- 7.8% and 32.9 +/- 10.6%), and alkalosis (32.1 +/- 10.3% and 36.1 +/- 17.0%) (p < 0.05). During pulmonary hypertension induced by N omega-nitro-L-arginine, the decreases in pulmonary arterial pressure and pulmonary vascular resistance produced by acetylcholine (9.6 +/- 6.4% and 23.9 +/- 14.1%, respectively) were significantly attenuated (p < 0.05), but the decreases produced by hyperoxia or alkalosis were unchanged. Therefore, hyperoxia and alkalosis can produce pulmonary vasodilation independent of EDNO synthesis in the intact newborn lamb.
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PMID:Hyperoxia and alkalosis produce pulmonary vasodilation independent of endothelium-derived nitric oxide in newborn lambs. 847 13


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