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)

In the fetal lamb, oxygen-induced pulmonary vasodilation is attenuated by the combined use of purinergic receptor P1 and P2y antagonists, which block the effect of adenosine and adenosine triphosphate (ATP), respectively, and by N(omega)-nitro-L-arginine [an inhibitor of endothelium-derived nitric oxide (EDNO) synthesis]. In the newborn lamb, oxygen-induced pulmonary vasodilation is not blocked by N(omega)-nitro-L-arginine. We investigated the role of ATP and adenosine in oxygen-induced pulmonary vasodilation in eight newborn lambs with pulmonary hypertension induced by the thromboxane mimic, U46619. The hemodynamic effects of hyperoxia, ATP, adenosine, sodium nitroprusside (SNP), and acetylcholine (ACh) were compared before and after purinergic receptor blockade with Cibacron blue (CB, a P2y-receptor antagonist) and 8-phenyltheophylline (8PT, a P1-receptor antagonist) individually, together, and on a separate day, after infusion of N(omega)-nitro-L-arginine. During pulmonary hypertension, combined pretreatment with 8PT and CB attenuated the decrease in pulmonary arterial pressure caused by hyperoxia (11.3 vs. 35.2%), ATP (10.6 vs. 32.2%), and adenosine (1.9 vs. 33.7%) without change in the effect of ACh or SNP (p < 0.05). N(omega)-Nitro-L-arginine attenuated the pulmonary vasodilation caused by ATP and ACh but not by hyperoxia, adenosine, or SNP. In the newborn lamb, the pulmonary vasodilating effect of both oxygen and ATP are attenuated by combined P1 and P2y purinergic-receptor antagonists. Postnatally, oxygen-induced pulmonary vasodilation appears to be mediated by ATP through purinergic receptors.
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PMID:Oxygen-induced pulmonary vasodilation is mediated by adenosine triphosphate in newborn lambs. 926 28

Hyperoxic lung injury is enhanced in isolated perfused lungs (IPL) in the presence of L-arginine. Reactive O2 species such as superoxide anion (O2-.) produced during hyperoxia are known to react with nitric oxide to form the strong oxidant species peroxynitrite. The appearance of O2-. in red blood cell membranes in vitro and in buffer-perfused lung preparations can be inhibited by the stilbene compound 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) DIDS also inhibits anion exchange across the cell membrane regulated by a family of anion exchange proteins (AE). In this study, we hypothesized that anion exchange inhibitors would prevent lung injury from hyperoxia and L-arginine (O2 + L-Arg) by decreasing O2-. flux into the vascular space of the IPL. We found that both DIDS and a structurally distinct anion transport blocker, dipyridamole, protected the rabbit IPL from pulmonary hypertension and edema produced by O2 + L-Arg. The protective effect was associated with increased nitrite concentrations in the perfusate. Protection also was conferred when sodium bicarbonate in the perfusion buffer was replaced with either sodium thiosulfate or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES). In lungs perfused with thiosulfate or HEPES-containing buffer, protection from O2 and L-arginine was also associated with diminished detection of reducing activity consistent with O2-. in the vascular space. Western blot analysis of lung protein and immunocytochemical staining of lung sections using antibodies against rabbit red blood cell AE1 and mouse gastric AE2 peptide showed that lung contains membrane protein antigenically similar to gastric AE2. These data suggest the possibility that inhibition of AE or other anion transporters may play an important role in mediating oxidative lung injury.
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PMID:Protection of perfused lung from oxidant injury by inhibitors of anion exchange. 927 40

The ability of atrial natriuretic peptide, salbutamol, sodium nitroprusside and isosorbide dinitrate to protect against challenge with methacholine in bovine isolated bronchi was compared in different O2 tensions. Perfusing the Krebs-Henseleit solution with gas mixtures containing 95% O2 (hyperoxia), 20% O2 (approximately normoxia) and 0% O2 (hypoxia) produced O2 tensions in the organ-baths of 524, 147 and 26 mm Hg, respectively. In hyperoxia, pre-incubation of atrial natriuretic peptide at concentrations of 3 x 10(-7) M and 10(-6) M significantly attenuated responses to methacholine, whereas in normoxia, these concentrations of atrial natriuretic peptide had no effect. Furthermore, in hypoxia, 3 x 10(-7) M and 10(-6) M atrial natriuretic peptide significantly enhanced responses to methacholine. Salbutamol, at concentrations of 3 x 10(-7) M and 10(-6) M significantly attenuated responses to methacholine in hyperoxia, whereas in normoxia and hypoxia, pre-incubation of salbutamol did not alter the methacholine response. Pre-incubation of 10(-5) M sodium nitroprusside significantly attenuated methacholine-induced contractions in hyperoxia and when the oxygen tension in the gas mixture was lowered to 20% or 0%, the ability of sodium nitroprusside to protect against methacholine challenge was enhanced. In hyperoxia, isosorbide dinitrate, at the 10(-4) M level, evoked a rightward shift of the methacholine response curve. Lowering the oxygen tension to either 20% or 0% enhanced the protectant effect of isosorbide dinitrate, with the effect being greater in 20% O2. Thus, the effect of these bronchodilators on methacholine-induced challenge in hyperoxia O2 differed from those in normoxia and hypoxia, although the direction of the changes varied among the agents used. This suggests that the responses evoked by bronchodilators in 95% O2 may not necessarily predict those in the physiological range of oxygen tensions and that the relative effectiveness of bronchodilators may vary between normoxic and hypoxic conditions.
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PMID:Changing the oxygen tension alters the ability of bronchodilators to protect against methacholine-induced challenge in bovine isolated bronchial rings. 934 33

Active Na+ transport by the alveolar epithelium keeps alveoli relatively dry. Hyperoxia increases epithelial permeability, resulting in pulmonary edema. We sought to determine whether active Na+ resorption from the air spaces and Na-K-ATPase activity increased in rats exposed to > 95% O2 for 60 h. The permeability x surface area products for unidirectional resorption of alveolar [14C]sucrose (PSsucrose) and 22Na+ (PSNa+) were measured in isolated, perfused rat lungs immediately after hyperoxia and after 3 and 7 days of recovery in room air. At 60 h of hyperoxia, the mean PSsucrose and PSNa+ increased from 6.71 +/- 0.8 x 10(-5) to 12.6 +/- 1.6 x 10(-5) cm3/s (P = 0.029) and from 23.6 +/- 1.1 x 10(-5) to 31.0 +/- 1.6 x 10(-5) cm3/s (P < 0.008), respectively. However, the values in individual rats ranged widely from no change to nearly a fourfold increase. Subgroup analysis revealed that benzamil- or amiloride-sensitive (transcellular) PSNa+ was significantly reduced in the exposed lungs with normal PSsucrose but was maintained in the lungs with high PSsucrose. By day 3 of recovery, mean Na+ and sucrose fluxes returned to values similar to control. Na-K-ATPase membrane hydrolytic maximal velocity (Vmax) activity fell significantly immediately after hyperoxic exposure but recovered to normal values by day 3 of recovery. The Na-K-ATPase beta 1-subunit antigenic signal did not significantly change, whereas the alpha 1-subunit levels increased during recovery. In summary, there was a heterogeneous response of different rats to acute hyperoxia. Hyperoxia led to complex, nonparallel changes in Na+ pump antigenic protein, hydrolytic activity, and unidirectional active Na+ resorption. Active Na+ transport was differentially affected, depending on degree of injury, but permeability and transport normalized by day 3 of recovery.
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PMID:Hyperoxic effects on alveolar sodium resorption and lung Na-K-ATPase. 943 74

Rats exposed to 85% O2 for 5-7 days develop tolerance to otherwise lethal hyperoxia (100% O2). The rate of alveolar fluid clearance increases during adaptation to hyperoxia, due in part to increased alveolar epithelial sodium channel activity. In these studies, we have investigated molecular mechanisms leading to increased lung Na+,K(+)-ATPase activity in hyperoxia. We exposed adult rats to 85% O2 (sublethal hyperoxia) for 7 days, followed by 2, 3, or 4 days in 100% O2. Steady-state levels of the Na+,K(+)-ATPase alpha 1 and beta 1 subunit mRNAs increased in whole lung tissue during hyperoxia exposures. Stability of the Na+,K(+)-ATPase alpha 1 and beta 1 subunit mRNA messages in whole lung RNA did not change significantly. Thus, lung Na+,K(+)-ATPase gene expression in sublethal hyperoxia appears to be regulated in part at the transcriptional level. Alveolar epithelial type II (ATII) cell Na+,K(+)-ATPase alpha 1 and beta 1 subunit proteins, measured by quantitative immunofluorescence, increased significantly after sublethal hyperoxia and 100% O2 exposures. Increases in lung fluid clearance after sublethal hyperoxia are associated with increased ATII cell Na+,K(+)-ATPase protein and whole lung Na+,K(+)-ATPase mRNA expression, which correspond to previously described increases in epithelial sodium channel expression under these conditions.
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PMID:Modulation of rat lung Na+,K(+)-ATPase gene expression by hyperoxia. 955 75

We studied the effects of the nitric oxide (NO) synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), and the NO donor, sodium nitroprusside (SNP) on cat chemosensory responses to intravenous injections of NaCN (0.1-100 microg/kg) and dopamine (0. 1-20 microg/kg), and to hyperoxic ventilation (100% O2, 60-120 s). Cats were anesthetized with sodium pentobarbitone, paralyzed and artificially ventilated to prevent secondary ventilatory effects. The frequency of chemosensory discharges (fx) was recorded from one sectioned carotid sinus nerve. L-NAME (50 mg/kg i.v.) increased basal fx and slightly potentiated the responses to NaCN and dopamine. SNP (1-2 mg/kg i.v.) increased basal fx, but reduced the NaCN-induced increases of fx over baseline and the transient fx inhibitions induced by dopamine, but not those produced by hyperoxia. Present results indicate that besides the known inhibitory effect of NO on chemosensory responses to low PO2, NO also blocks the chemosensory response to dopamine, leaving hyperoxic responses largely unchanged.
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PMID:Sodium nitroprusside blocks the cat carotid chemosensory inhibition induced by dopamine, but not that by hyperoxia. 966 65

The gene expression of heme oxygenase-1 (HO-1) was studied in mammalian cell lines exposed to hyperoxia. Northern blot analysis demonstrated that hyperoxic exposure increased the HO-1 mRNA levels in various types of cells, including human hepatoma (HepG2) cells. This increase was time- and dose-dependent, and reversible. The HO-1 mRNA levels in HepG2 cells were increased to 2.3- and 4.2-fold of the control by hyperoxic exposure of 6 and 23 h, respectively. Cycloheximide and actinomycin D inhibited the increases in the HO-1 mRNA level produced by hyperoxia, indicating that response to hyperoxia is dependent on de novo protein synthesis and mRNA transcription. Antioxidants, desferrioxamine (DES) and o-phenanthroline (OP) partially inhibited the HO-1 mRNA elevation by hyperoxia. In addition to hyperoxia, sodium arsenite (NaAsO2), cadmium chloride (CdCl(2)) and hydrogen peroxide (H2O2), which are reactive oxygen intermediates (ROI) generators, increased the HO-1 mRNA level by 11-, 22- and 2.5-fold, respectively. OP, an antioxidant and a bivalent metal chelator, blocked the HO-1 mRNA elevation induced either by hyperoxia or by the three ROI generators. In contrast to OP, N-acetylcysteine (NAC), an antioxidant and membrane-permeable reducing reagent, enhanced the HO-1 mRNA elevation induced by hyperoxia, although NAC inhibited the mRNA elevation induced by NaAsO2, CdCl2 and H2O2. These results indicate that oxygen tension regulates HO-1 gene expression and suggest that hyperoxia-specific and redox-sensitive regulators may be involved in hyperoxia-mediated HO-1 gene expression.
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PMID:Oxygen tension regulates heme oxygenase-1 gene expression in mammalian cell lines. 974 10

The lung epithelium resorbs alveolar fluid through combined action of sodium channels and the sodium pump, Na,K-ATPase. The lung often is exposed to hyperoxia in disease states and hyperoxia generates a mixture of reactive oxygen species. In vivo and in vitro exposure of rat lung and alveolar type II cells, respectively, increases gene expression of both alpha-1 and beta-1 subunits of the sodium pump. In contrast to the primary type II cells, several type II cell lines did not increase sodium pump gene expression with hyperoxia, but the renal tubular epithelial MDCK cell line did. Using promoter-receptor constructs transfected into MDCK cells, hyperoxia did not markedly increase transcription of the alpha-1 subunit but doubled transcription of the beta-1 subunit gene. Using 5'-deletion constructs, the region required for the beta-1 increase was localized to a 40-base pair region from -44/-84. The hyperoxic responsiveness of this region was confirmed using constructs with one or two copies of this region placed in minimal promoter-luciferase reporters. This 5' promoter region contains a consensus binding sequence for SP-1, a basal transcription factor but not for binding of other known transcription factors. Thus, hyperoxia induces Na,K-ATPase beta-1 promoter transcription, likely acting through a novel mechanism.
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PMID:Oxidant effects on epithelial Na,K-ATPase gene expression and promoter function. 978

Heme oxygenase 1 (HO-1), a stress response protein, is highly induced in response to various agents causing oxidative stress including ultraviolet irradiation, sodium arsenite, hyperoxia, and glutathione depletors. We recently characterized the induction of HO-1 gene expression by nitric oxide (NO) and postulated that the addition of an antioxidant, such as pyrrolidine dithiocarbamate (PDTC), would attenuate HO-1 induction in response to NO. Surprisingly, PDTC was a very potent inducer of HO-1 gene expression, causing increases in the steady-state level of HO-1 mRNA in rat aortic vascular smooth muscle (aVSM) cells in a time- and concentration-dependent manner. PDTC-induced HO-1 gene expression correlated with a rise in protein levels and was dependent on both increased gene transcription and mRNA stability. Deletional analyses of the proximal promoter and the entire 5' distal upstream region of the HO-1 gene (11 kbp) were performed including the two 5' distal enhancers, SX2 and AB1, located 4 kbp and 10 kbp upstream of the transcription site, respectively. Plasmid vectors containing various fragments of this region were linked to a chloramphenicol acetyl transferase (CAT) reporter gene, stably transfected into RAW 264.7 cells, and transfectants were assayed for CAT activity after treatment with PDTC. We show that the AB1 distal enhancer plays an important role in mediating PDTC-induced HO-1 gene transcription. Mutational analyses of this enhancer showed that the activator protein 1 (AP-1) regulatory element is crucial for PDTC-induced HO-1 gene transcription. Electrophoretic mobility shift assays supported this data, demonstrating increased AP-1 DNA binding activity after PDTC treatment. Taken together, our data demonstrate that the antioxidant PDTC enhances HO-1 gene transcription and that the induction appears to be mediated by AP-1 activation of regulatory elements specific to the distal enhancer AB1.
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PMID:Transcriptional regulation of the heme oxygenase 1 gene by pyrrolidine dithiocarbamate. 983 57

1. It has been widely accepted that the rat aortic depressor nerve contains only baroreceptors. However, the experiments which have provided these negative data have employed whole aortic nerve recording. In the present study, the technical difficulties associated with recording single fibres in vivo, from the rat aortic nerve (diameter 25-50 microm), have been surmounted using a small tip, glass suction electrode technique. 2. Upon switching from normocapnic hyperoxia to hypercapnic hypoxia, irregularly firing units (n = 13) appeared and these were significantly excited by intravenous injections of sodium cyanide (20 microg) but not by rises in arterial blood pressure induced by methoxamine (an alpha1-adrenoreceptor agonist; 10 microg). Inhalation of 100 % oxygen rapidly and reversibly silenced, or profoundly reduced, ongoing activity. 3. Intravenous injection of phenylbiguanide (PBG; a 5-HT3 receptor agonist; 8 microg) strongly stimulated the chemoreceptors and was followed by a period of chemodepression (3-21 s). In contrast none of the single fibre baroreceptors recorded (n = 15) were excited by PBG but all significantly increased their discharge in response to the increases in arterial blood pressure associated with methoxamine and cyanide. Both the excitatory and inhibitory effects of PBG on the chemoreceptor fibres were abolished by ondansetron (a 5-HT3 receptor antagonist: 1 mg kg-1 i.v.; n = 5 animals) whilst the chemoexcitatory action of cyanide was preserved. 4. It is concluded that there are chemoreceptor afferents contained in the aortic nerve of the Sprague-Dawley rat. The 5-HT3 receptor appears not to be a pre-requisite for aortic body chemoexcitation.
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PMID:Activity of aortic chemoreceptors in the anaesthetized rat. 988 53


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