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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Age-related changes in pulmonary formation of arachidonic acid (AA) metabolites are thought to play an important role in regulating cardiopulmonary function. This study addresses the potential role of reduced glutathione (GSH) in modulating cyclooxygenase product formation in the developing lung. Prostaglandin H2 (PGH2) metabolism was studied in microsomal fractions isolated from the lungs of unventilated fetal, neonatal and adult goats. GSH-dependent PGH2 to PGE2 isomerase activity in microsomal fractions from the perinatal (fetal and neonatal) goat lung was not saturable with respect to GSH and can respond to changes in GSH concentration over the range of 0.01 to 30 mM, which encompasses the full range the intracellular GSH levels reported in the literature. However, in fractions from the adult, a lower rate of PGE2 formation is observed at higher GSH concentrations. In addition, the tissue levels of GSH exhibited developmental stage-related differences with fetal being higher than neonatal or adult. The present observations may have physiologic relevance, in that decreases in pulmonary GSH levels after birth may contribute to decreases in plasma PGE2 levels by decreasing pulmonary PGE2 synthesis, thereby contributing to closure of the ductus arteriosus; conversely, increased GSH levels associated with hyperoxia may contribute to persistence of ductal patency. Formation of 6-keto-PGF1 alpha and of TXB2 (the stable metabolites of prostacyclin and TXA2) was decreased when PGE2 formation was increased by GSH activation of PGE2 isomerase in fractions isolated from all three developmental stages. A similar pattern of product formation was observed when AA was employed as substrate. These data suggest the possibility that changes in GSH concentration may modulate eicosanoid formation in cells that contain GSH-dependent PGE2 isomerase, as well as either or both prostacyclin or thromboxane synthase(s).
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PMID:Concentration-activity profile of the modulation of cyclooxygenase product formation by reduced glutathione in microsomal fractions from the goat lung. 211 78

Prostaglandins (PGs) have been implicated in the development of pulmonary oxygen toxicity. We tested the hypothesis that hyperoxia modulates PG synthesis in a differentiation-arrested primary lung cell culture model in the rat at three developmental ages: day-20 gestation (term = 22 days), days 1 and 3 after birth. The time courses of the response to hyperoxia were defined in preconfluent lung cells as well as in growth-arrested, confluent cells. From days 4-8 after plating in growth medium containing 10% carbonstripped fetal bovine serum, exposure to 95% O2, in contrast to 1% O2, inhibited cell proliferation but significantly enhanced the production of PGI2 and, to a lesser extent, PGE2 at all three ages. The capacity to metabolize exogenous arachidonic acid (AA) to PGI2 was also increased two-to threefold (P less than 0.01). Cellular release of lactate dehydrogenase, a measure of O2 toxicity, remained unchanged during exposure to 1% O2 but increased fivefold between 48 and 96 h after exposure to hyperoxia (from 2% total to 10.5%, P less than 0.01). In confluent, growtharrested cells, under serum-free conditions, exposure to hyperoxia for 24-48 h resulted in a similar induction of PG synthesis. Our results suggest that hyperoxia stimulates PG synthesis in the perinatal rat lung and that this effect is independent of cell growth or the presence of serum. We speculate that this hyperoxia-induced PG synthesis is a relatively early response to oxidant stress and may serve as an useful early marker for O2 toxicity in perinatal lung cells.
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PMID:Stimulation of prostaglandin synthesis by hyperoxia in perinatal rat lung cells. 211 34

We compared oxygen-related prostaglandin synthesis in fetal lamb ductus arteriosus (DA) pulmonary artery (PA) and aorta endothelial and smooth muscle cells. We measured basal synthesis of 6-keto-PGF1 alpha and PGE2, the response to calcium ionophore (A23187), a nonspecific stimulus of prostaglandin production, as well as the response to oxygen, a perinatal stimulus, monitoring both the effects of hyperoxia (95% O2) and hypoxia (2% O2). In addition, we established whether differences observed in fetal lamb PA cells related to oxygen tension were also observed in newborn central and microvessel PA cells. Our results indicate that DA endothelial cells increase 6-keto-PGF1 alpha in response to ionophore (p less than 0.05). With hyperoxia, DA endothelial cells increase PGE2 synthesis and DA smooth muscle cells increase 6-keto-PGF1 alpha (p less than 0.05 and 0.02, respectively). Aorta smooth muscle cells increase 6-keto-PGF1 alpha in response to ionophore and hyperoxia (p less than 0.003 and 0.05, respectively). PA endothelial and smooth muscle cells have higher levels of basal prostaglandin synthesis when compared with DA and aorta. In response to ionophore, increased 6-keto-PGF1 alpha is observed in both PA endothelial and smooth muscle cells (p less than 0.02 and 0.0004, respectively), and PGE2 is increased in PA smooth muscle cells (p less than 0.003). Hypoxia, however, decreases PA smooth muscle production of both 6-keto-PGF1 alpha and PGE2 (p less than 0.02 and 0.01, respectively). Similar observations were made in newborn lamb central and microvessel PA cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen-related prostaglandin synthesis in ductus arteriosus and other vascular cells. 250 51

To further study the role of arachidonic acid metabolites in the development of hyperoxic lung injury and the function of PMNs and/or alveolar macrophages in facilitating this role, we exposed adult rabbits to greater than 95% O2 or air for 24, 40, 48, or 65 hours. At the end of each study, bronchoalveolar lavage [BAL] of the left lung was performed, and the right lung was inflated and fixed for light and electron microscopy. PGE2, 6-keto-PGF1 alpha and thromboxane B2 were measured by RIA in arterial and venous plasma at the beginning and end of each study and in BAL fluid obtained at sacrifice. Production of these three PGs by BAL cells placed in cell culture was also measured. Significant hyperoxic lung injury did not develop until 65 hours, as evidenced by significant increase in BAL total protein and percent PMNs, and by morphologic findings. At 40 hours, however, BAL fluid PGE2 and 6-keto-PGF1 alpha increased and BAL cell production of all 3 PGs was significantly increased (p less than .05). In summary, the early PG increases observed in these studies may directly contribute to the development of hyperoxic lung injury or, rather, may be representative of a generalized increase in all arachidonic acid metabolites, including the lipoxygenase pathway. The increase in BAL cell PG production and increased PG concentrations in BAL fluid prior to any increase in BAL PMNs suggest that the AM may be the source of the early arachidonic acid metabolite increase in response to hyperoxia.
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PMID:The early involvement of pulmonary prostaglandins in hyperoxic lung injury. 310 36

Prostanoid formation in human umbilical vessels perfused in vitro was assessed at different oxygen tensions. At an atmosphere of 5% oxygen the production rate of prostacyclin (measured as 6-keto-PGF1 alpha) was higher, while those of thromboxane A2 (measured as TXB2), PGE2 and PGF2 alpha were lower than with 20%, 50% and 95% oxygen. The stimulatory effect of angiotensin II on prostanoid production was found to be independent on the prevailing oxygen tension. Vascular formation of prostanoids thus seems to be at least partially affected by the ambient oxygen tension. Though altered oxygen tension does not seem to affect angiotensin induced prostanoid formation, the action of other vasoactive agents influencing vascular formation of prostanoids may respond differently to hypoxia or hyperoxia.
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PMID:Altered prostanoid formation in human umbilical vasculature in response to variations in oxygen tension. 343 54

Exposure of rats to high concentrations of oxygen (greater than 95%) at 1 ATA pressure (101 kPa) is lethal within three days. Rats treated with a small dose of endotoxin are protected against these lethal effects of hyperoxia. Recently, we found that the lysine salt of acetylsalicylic acid antagonises this protective action of endotoxin. This suggests that prostaglandin metabolism plays an important role in the protective action of endotoxin against pulmonary oxygen toxicity. Therefore, we measured the plasma levels of 6KPGF1 alpha, a stable degradation product of prostacyclin (PGI2), PGE2 and thromboxane B2, the stable degradation product of thromboxane A2, in rats exposed to air or greater than 95% oxygen for 48 hours. We compared these with the plasma levels of rats treated with endotoxin (Salmonella typhimurium lipopolysaccharide 1 mg/kg) and exposed to air or greater than 95% oxygen for 48 hours. We found that exposure of rats to greater than 95% oxygen for 48 hours leads to a significant rise in the 6KPGF1 alpha levels. Rats exposed to greater than 95% oxygen for 48 hours and treated with endotoxin had significantly higher PGE2 and significantly lower 6KPGF1 alpha plasma levels than saline-treated rats exposed to greater than 95% oxygen for 48 hours.
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PMID:Endotoxin protection against pulmonary oxygen toxicity and plasma prostaglandin levels in the rat. 347 92

Prostaglandin metabolism by rat lung tissue was measured following exposures of 6, 24 and 48 hours to either pure oxygen or air at one atmosphere. Tissue concentrations of PGE1, PGE2 and PGF2 alpha were not altered by oxygen exposures. Prostaglandin synthetase activity decreased between 24 and 48 hours but was not significantly different from control at 48 hours. Combined prostaglandin dehydrogenase/reductase activity decreased between 24 and 48 hours to 13% of control values and was significantly lower than in air at 48 hours. The plasma concentration of 13, 14 dihydro-15-keto PGF2 alpha, a catabolite of PGF2 alpha, was significantly lower in oxygen-exposed rats at 24 and 48 hours. We conclude that endogenous pulmonary prostaglandin concentrations are maintained during hyperoxia but that catabolism of prostaglandins by the lungs may be impaired.
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PMID:Pulmonary prostaglandin metabolism during normobaric hyperoxia. 626 Dec 83

The effect of a previous exposure to hyperbaric oxygen (HBO) on the synthesis capacity of prostaglandin (PG) and thromboxane (TX) was investigated in the brain of male rats. Three groups of rats were used: 1. Neurotoxic HBO (n = 11): The rats were exposed to sixfold the atmospheric pressure (101.3 kPa), i.e., 6 absolute atmospheres (ATA), of pure O2 up to the first convulsion (6 ATA O2); 2. Mild hyperoxia (n = 10): The rats were exposed to compressed air at the same absolute pressure and for a similar time than that of the neurotoxic HBO group (here PO2 is 1.26 ATA); 3. Normoxia at atmospheric pressure (PO2 is 0.21 ATA) for control. There was no convulsion in groups 2 and 3. Decompression of the high pressure groups lasted 15 min. After decapitation, samples of the frontal cortex and the striatum were taken, weighed, washed, and then incubated in Krebs-Ringer bicarbonate for 1 h. The release of eicosanoids in the medium was determined by enzyme immunoassay. Mild hyperoxia only significantly reduced in the striatum the release of 6-keto-PGF1 alpha (1.3 +/- 2.4 vs 10.9 +/- 6.6 pg/mg wet tissue, p < 0.001; mean +/- SD) and PGE2 (3.2 +/- 2.7 vs 7.8 +/- 6.5 pg/mg wet tissue, p < 0.05), whereas TXB2 did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of hyperbaric oxygen on prostaglandin and thromboxane synthesis in the cortex and the striatum of rat brain. 829 21

We examined the effect of hyperoxia on arachidonic acid (AA) metabolism in bovine carotid artery endothelial cells (CAEC) and pulmonary artery endothelial cells (PAEC). Confluent monolayers were exposed to hyperoxic gases (95% O2 or 60% O2) from 12-72 h. Control cells were incubated under normoxic condition (air-5% CO2). After exposure of the cells to normoxic or hyperoxic conditions, prostaglandin (PG) synthesis activity was analyzed in cell homogenates using thin layer chromatography; release of 6-keto-PGF1 alpha, a stable metabolite of PGI2, into the culture medium was measured using a radioimmunoassay. The major metabolites formed from exogenously supplied 14C-AA were 6-keto-PGF1 alpha and a small amount of PGE2. Hyperoxia (95% O2) decreased the synthesis of these cyclooxygenase products beginning at 24 h; moderate hyperoxia (60% O2) had no such effect. There was no significant difference between CAEC and PAEC with respect to the depletion effect of hyperoxia. After 72 h of exposure to 95% O2, endothelial injury was observed in CAEC but not in PAEC. We conclude that hyperoxia decreases cyclooxygenase activity in endothelial cells, and that this decrease is dependent on the severity of the hyperoxia. In addition, CAEC are more susceptible to hyperoxia-induced injury than PAEC. The depletion of cyclooxygenase activity and the resultant effect on PGI2 and PGE2 production may be a factor in the development of hyperoxia-induced endothelial injury.
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PMID:Hyperoxia decreases cyclooxygenase activity in endothelial cells. 834 23

The aim of this study was to examine the effects of asphyxia-reventilation and hyperoxia on the cerebral blood perfusion and prostanoid production of the brain arteries and microvessels in piglets. After 10 min of asphyxia, animals were ventilated with room air, or with 100% O2. Following 4 hours of recovery, the brains were perfused, cerebral arteries were removed and microvessels were isolated from the cortex. The microvessels and the arteries were incubated with 1-14C-arachidonic acid, and the 1-14C-prostanoids were then separated by means of overpressure thin-layer chromatography and were quantitatively determined. Under control conditions, the synthesis of dilatory prostanoids dominated the arachidonate cascade both in the microvessels and in the arteries. Asphyxia and reventilation with room air did not modify the prostanoid production. O2 ventilation greatly affected the prostanoid synthesis of the microvessels, with an enhancement of PGD2 up to 247 +/- 27%. In the arteries, the production of PGI2 and of PGE2 was elevated to 272 +/- 15% and to 148 +/- 13%, respectively. These findings indicate that O2 ventilation after asphyxia substantially increases the extent of prostanoid synthesis in the cerebral blood vessels.
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PMID:Prostanoid synthesis in the cerebral blood vessels of asphyxiated piglets. 1199 9


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