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

1. The influence of some drugs which affect the dopaminergic system was studied on chemosensory responses to dopamine (DA), acetylcholine (ACh), sodium cyanide NaCN) and hypoxia during experiments on pentobarbitone anaesthetized cats in which chemoreceptor activity was recorded from the peripheral end of a sectioned sinus nerve. 2. Spontaneous chemosensory activity was inhibited in a dose-dependent manner by DA (0.5-5 microgram, I.A.). Higher doses (10-50 microgram) caused a delayed increase in discharge and were associated with inconsistent inhibitory responses. 3. The DA antagonist alpha-flupenthixol (0.2 mg/kg, I.A.) blocked the inhibitory response to DA without affecting either the spontaneous discharge frequency or the response to ACh. The effect of NaCN was potentiated, and during hypoxia chemoreceptor activity increased more rapidly, although the maximum frequency attained was not appreciably different from control values. Similar results were obtained with haloperidol (0.5 and 1.0 mg/kg, I.V.). 4. Higher doses of alpha-flupenthixol (0.5-1.0 mg/kg, I.A.) increased spontaneous chemoreceptor activity, but this was regarded as a non-specific effect of the drug since at these doses the inhibitory effect of 5-hydroxytryptamine (5-HT) was also abolished. 5. The animals were exposed to alternate periods of hypoxia and hyperoxia following administration of the tyrosine hydroxylase inhibitor alpha-methyl p-tyrosine (AMPT, 0.2-10 mg/kg, I.A.). The inhibitory response previously evoked by amphetamine was abolished, and electron microscopic studies showed a great reduction in the number of dense-cored granules, both of which suggested that DA levels in the carotid body had been substantially reduced. Responses to NaCN and hypoxia were slightly potentiated following AMPT, but neither spontaneous activity nor the response to ACh was affected. 6. Apomorphine (0.05-0.2 mg/kg, I.A.) inhibited the chemoreceptor discharge for up to 45 min, an effect which was antagonized by alpha-flupenthixol (0.2 mg/kg, I.A.), implying it resulted from DA receptor stimulation. Although responses to NaCN, hypoxia and higher doses of ACh were reduced following administration of apomorphine, the reduction was not very marked. 7. These results are not compatible with the theory of Osborne & Butler (1975), that in normoxia DA is tonically released in the carotid body and suppresses spontaneous chemosensory activity. 8. It is concluded that DA modulates chemosensory activity by influencing the rate of increase in discharge, without affecting maximum discharge frequency. The mechanism whereby DA is released in response to increased chemosensory activity remains to be established.
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PMID:Inhibitory action of dopamine on cat carotid chemoreceptors. 67 58

The effect of hyperoxia (1-14 days, 85% O2) on rat alveolar macrophage and alveolar type II cell oxidant and antioxidant characteristics was investigated. Unstimulated control macrophages (2 h ex vivo) released hydrogen peroxide at a rate of 3.5 +/- 1.3 nmol/min mg protein-1, which was a cyanide-sensitive process. H2O2 release from alveolar macrophages decreased slightly but not significantly after 1 day in hyperoxia and increased significantly after 3 days (180%, p less than .05) and 14 days (380%, p less than .01). When H2O2 release was expressed as nmol from total macrophages per animal, the increase after 14 days in hyperoxia was 760%. H2O2 generation by hyperoxic macrophages was cyanide resistant, indicating the involvement of active NADPH oxidase. In both control and hyperoxic macrophages H2O2 release could be significantly stimulated with phorbol myristate acetate (PMA). Comparisons of H2O2 release by freshly isolated alveolar macrophages and alveolar type II cells must be cautiously interpreted because some cell functions may change during the isolation procedure. Freshly isolated (6 h ex vivo) control alveolar type II cells were found to generate H2O2 at a rate of 0.26 +/- 0.05 nmol/min mg protein-1. In type II cells H2O2 release, calculated as nmol/mg protein, decreased during the first 7 days of hyperoxia to 10% (p less than .01) of the control value and then returned back up to the control level after 14 days. A similar decrease was observed if H2O2 release was calculated as nmol/cell number. H2O2 release from control and hyperoxic type II cells was cyanide sensitive. The decrease in H2O2 release in type II cells was associated with cell membrane injury (as assessed by electron microscopy), while biochemical markers of cellular injury (trypan blue exclusion and cellular high-energy phosphates ATP, ADP) were unchanged. The ability of type II cells to scavenge extracellular H2O2 did not change in acute hyperoxia, but it increased significantly during the second week in hyperoxia. These results indicate that macrophages but not type II cells are stimulated to produce H2O2 during prolonged exposure to hyperoxia.
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PMID:Hydrogen peroxide release from alveolar macrophages and alveolar type II cells during adaptation to hyperoxia in vivo. 139 11

Carotid body chemosensory response to hypoxia is attenuated as a result of prolonged normobaric hyperoxia (NH) in the cat. The effect of NH is likely to be due to high cellular PO2 and O2-related free radicals. Accordingly, the effect would be less if O2 delivery to the chemoreceptor tissue could be compromised. The aortic bodies, which appear to have less of a circulatory O2 delivery, as suggested by their vigorous responses to a slight compromise of O2 flow compared with those of the carotid body, could provide a suitable testing material for the hypothesis. We tested the hypothesis by studying both aortic and carotid body chemoreceptors in the same cats (n = 6) which were exposed to nearly 100% O2 for about 60 h. These chemoreceptor organs were also studied in 6 control cats which were maintained in room air at sea-level. The cats were anesthetized and their carotid and aortic chemosensory fibers were identified by the usual procedure, and their responses to hypoxia and hypercapnia and to bolus injections (i.v.) of cyanide and nicotine were measured. In the NH cats, the carotid but not aortic chemosensory responses to hypoxia and cyanide were attenuated and to hypercapnia (both onset and steady state) augmented. The aortic chemoreceptors were stimulated by hypoxia, hypercapnia, cyanide and nicotine both in the NH and the control cats similarly. The results support the hypothesis that it is presumably a higher tissue blood flow and hence a higher concentration of O2-related free radicals which ultimately led to the specific attenuation of O2 chemoreception in the carotid body.
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PMID:Aortic and carotid body chemoreception in prolonged hyperoxia in the cat. 178 Jun 2

Microscopic fluorometry was used to examine the effects of anoxia and cyanide (CN-) on cytosolic calcium [Ca2+]i of cultured carotid body (CB) glomus cells from newborn rabbits. Applications of high K+ and veratridine (VRT), a sodium channel activator, induced rapid and marked increases in [Ca2+]i. These effects were inhibited by D600 a calcium channel blocker. [Ca2+]i changes induced by VRT were also blocked by tetrodotoxin (TTX). Glomus cells exhibited a slow increase in [Ca2+]i in response to anoxia and CN-, and a slight decrease during hyperoxia. The effects of anoxia and CN- were blocked by D600 but not by TTX. We conclude that these stimuli induce calcium entry into glomus cells via voltage-dependent Ca2+ channels. Voltage-dependent Na+ channels were not involved.
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PMID:Response of cytosolic calcium to anoxia and cyanide in cultured glomus cells of newborn rabbit carotid body. 191 62

Chemical control of respiration in cats after chronic normobaric hyperoxia (NH; inhalation of 100% O2 for 60-67 h) was compared with that of control rats, anesthetized with pentobarbital. After chronic hyperoxia, induction of moderate hypoxia (PaO2 = 50-60 Torr) increased inspiratory time (TI) often without increasing tidal volume (VT). More intense hypoxia (PaO2 = 40-50 Torr) depressed tidal volume and further increased TI, diminishing the respiratory drive (VT/TI). Hypercapnia, on the other hand, increased tidal volume and shortened respiratory cycle time; but these responses were subnormal. The normal stimulatory effects of intravenous nicotine and inhibitory effect of dopamine on carotid chemo-receptor activity and ventilation were preserved in the NH cats. Cyanide, however, did not stimulate carotid chemoreceptor activity and ventilation. Thus, the changes in the carotid and aortic chemosensory activities elicited appropriate reflex ventilation responses, indicating that the central component of the chemoreflex was not impaired. The ventilatory depression during hypoxia despite an active chemosensory input is consistent with the lack of carotid chemosensory response to and a central depressant effect of hypoxia in the NH cats, and was presumably associated in part with an increased responsiveness of airway reflexes. We conclude that chronic hyperoxia selectively attenuated carotid chemosensory and chemoreflex responses to hypoxia.
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PMID:Chemical respiratory control in chronically hyperoxic cats. 207 96

The hypothesis that augmentation of the carotid chemoreceptor response to hypoxia by almitrine is due in part to an increased response to CO2 was tested by using single or few fiber preparation of carotid body chemosensory fibers in 12 cats anesthetized with alpha-chloralose. To differentiate between the plausible mechanisms of effects, we also tested the responsiveness of the afferents to cyanide and nicotine before and after almitrine. After a saturation dose of almitrine (1 mg.kg-1 followed by 0.5 mg.kg-1.h-1) the chemosensory responses to CO2 strikingly increased even during hyperoxia: the afferents showing an increased transient peak activity at the onset of hypercapnia, an augmented steady-state response to CO2 stimulus, and a decreased arterial PCO2 stimulus threshold. Thus, the effect of almitrine on carotid chemoreceptor response to hypoxia could be explained, at least in part, by its multiplicative stimulus interaction with CO2. After almitrine, the chemoreceptor response to cyanide, which is dependent on arterial PO2, was not particularly augmented relative to those of nicotine. Accordingly, the O2-sensing mechanism does not appear to be the primary site of almitrine effect. The results also indicate that the site of CO2 chemoreception resides downstream from those of hypoxia.
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PMID:Stimulus interaction between CO2 and almitrine in the cat carotid chemoreceptors. 256 54

By culturing HeLa cells at stepwise increased oxygen tensions over a prolonged period of time (approximately 21 months) we selected a substrain capable of growing under 80% O2/19% N2/1% CO2, an oxygen level that is lethal to normal HeLa cells, adapted to 20% O2/79% N2/1% CO2. The 80% O2-adapted cells exhibited the following characteristics. At the ultrastructural level an abnormal mitochondrial morphology was observed: compared to normal cells, mitochondria of the hyperoxia-adapted cells exhibited a 3-fold larger mean profile area in sections and were slightly decreased in number; the relative mitochondrial volume was increased 2-fold, whereas the size of both cell types was the same. Mitochondrial matrix appeared less dense in the hyperoxia-adapted cells; no structural damage was detected. Compared to the 20% O2-adapted cells O2 consumption per cell was approximately 40% decreased in the 80% O2-adapted cells. Under hyperoxic conditions 20% O2-adapted and 80% O2-adapted cells exhibited very similar cyanide-resistant respiration rates (0.16 +/- 0.04 and 0.15 +/- 0.02 fmoles/cell/minute, respectively), suggesting that the increased O2 tolerance of the 80% O2-adapted cells was not due to a decreased cellular production of activated oxygen species at hyperoxia. Cellular levels of the enzymes directly involved in protection against activated oxygen species, i.e., superoxide dismutases, catalase, and glutathione peroxidase, were normal or slightly below normal in the 80% O2-adapted cells, implying that these enzymes were of no significance for the increased O2 tolerance. In addition, the specific activity of glucose-6-phosphate dehydrogenase, a key enzyme for cellular production of NADPH, was not related to the degree of O2 tolerance. Our results suggest that the increased O2 tolerance of the 80% O2-adapted cells is neither based on cellular properties controlling the formation or removal of intracellular activated oxygen species nor on the cellular capacity to repair or replace damaged cellular components. We speculate that the increased O2 tolerance is largely due to a genetically determined increased resistance of oxygen-sensitive cellular targets.
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PMID:Some characteristics of hyperoxia-adapted HeLa cells. A tissue culture model for cellular oxygen tolerance. 298 61

The effects of normobaric hyperoxia on carotid body chemosensory function in the cat were studied. The hypothesis was that carotid body chemosensory function would be affected by chronic exposure to 100% O2 at sea level. It was based on the assumptions that carotid body tissue is exposed to high PO2 because of its high blood flow and that its O2 chemosensing mechanism is sensitive to O2 radical-induced reactions. Twelve cats were exposed to 100% O2 for 60-67 h, and 10 control cats were maintained in room air at sea level. They were anesthetized with pentobarbital sodium (Nembutal), and chemosensory afferents from a cut carotid sinus nerve were isolated and identified. The responses of single or a few clearly identifiable chemoreceptor afferents to isocapnic hypoxia and hypercapnia during hyperoxia and to the bolus injections of cyanide, nicotine, and dopamine were studied. We found that chronic hyperoxia severely blunted or eliminated the O2-sensitive response of the carotid chemoreceptors while augmenting the hypercapnic response. The response to cyanide but not to nicotine and dopamine were attenuated. Thus the hypoxic and hypercapnic responses that normally interact were separable. The lack of the cyanide response was consistent with the lack of the hypoxic response, suggesting a possible shared mechanism of carotid chemoreceptor response. Qualitatively normal responses to dopamine and nicotine indicated that the respective receptors were relatively intact after chronic exposure to hyperoxia and that the sensory nerves themselves were not affected by the prolonged O2 exposure.
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PMID:Carotid body chemosensory function in prolonged normobaric hyperoxia in the cat. 311 Jan 24

Hypercapnia attenuates the effects of static airway pressure (Paw) on phrenic burst frequency (f) and the expiratory duration (TE) in chloralose-urethan-anesthetized dogs. Surgical removal of the carotid bodies abolishes this interaction. Since halothane anesthesia in hyperoxia greatly impairs peripheral chemoreflexes, experiments were conducted to determine whether hypercapnia would attenuate the effects of Paw on f and TE in halothane-anesthetized dogs (approximately 1.5 minimum alveolar concentration). Integrated activity of the phrenic nerve was monitored as a function of Paw (2-12 cmH2O) in a vascularly isolated left lung at varied levels of arterial PCO2 (PaCO2; 38-80 Torr) controlled by inspired gas concentrations ventilating the denervated but perfused right lung. Halothane was administered only to the right lung. The results were as follows: 1) integrated phrenic amplitude increased with PaCO2 but was unaffected by Paw; 2) f decreased as Paw increased but was not affected by PaCO2; 3) the inspiratory duration (TI) increased as PaCO2 increased but was unaffected by Paw; 4) TE increased as Paw increased but was unaffected by PaCO2; and 5) there was no phrenic response to intravenous sodium cyanide (50-100 micrograms/kg). Thus, unlike chloralose-urethan-anesthetized dogs, hypercapnia does not attenuate the effect of lung inflation on f or TE in halothane-anesthetized dogs. Furthermore, hypercapnia increases TI during halothane anesthesia, an effect found after carotid denervation but not found in intact chloralose-urethan-anesthetized dogs. It is suggested that these differences between chloralose-urethan- and halothane-anesthetized dogs may be due to functional carotid chemoreceptor denervation by halothane.
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PMID:Ventilatory responses to lung inflation and arterial CO2 in halothane-anesthetized dogs. 313 47

Further characteristics of an oxygen-tolerant variant of Chinese hamster ovary cells (CHO-99) capable of stable proliferation at 99% O2/1% CO2, and O2 level that is lethal to the parental line (CHO-20), are described. Previous work has revealed that CHO-99 cells have 2- to 4-fold increased activities of superoxide dismutases, catalase and glutathione peroxidase, and substantially increased relative volumes of mitochondria and peroxisomes. To document possible additional mechanisms of O2 tolerance we compared CHO-20 cells growing at 20% O2 (normoxia) and CHO-99 cells at 99% O2 (normobaric hyperoxia). We show the following: (1) the estimated total (oxidative and glycolytic) ATP production in CHO-99 cells was 36% decreased. ATP production through oxidative phosphorylation was 52% lower in CHO-99 cells, while the relative contribution from glycolysis was increased from 6% to 30%. The ATP content was 29% lower in CHO-99 cells, the adenylate energy charge being also significantly decreased, indicating that energy production through oxidative phosphorylation is compromised in CHO-99 cells. Cyanide-resistant respiration was 4-fold higher in CHO-99 cells, probably reflecting, at least partly, the increased peroxisomal activity in these cells. (2) The level of reduced glutathione was several fold increased in CHO-99 cells, oxidized glutathione being unaltered; (NADPH + NADP+) levels were elevated 2.7-fold, while the ratio of NADPH to NADP+ was increased almost two-fold. These changes were associated with a 50% increased metabolism of glucose through the hexose monophosphate pathway. (3) No evidence was obtained for an increased steady-state level of endogenous lipid peroxidation in CHO-99 cells, in spite of a 50% increased content of polyunsaturated fatty acids in the phospholipid fraction.
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PMID:Characterization of oxygen-tolerant Chinese hamster ovary cells. II. Energy metabolism and antioxidant status. 338 44


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