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)

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

It seems clear that the abundance of potential treatment options reflects the dearth of proved, effective options. Thus, although we appear to be on the brink of many potentially major breakthroughs in treatment, there currently remains a multitude of unanswered questions and the need for further study. At this point clinical recommendations must be limited to supportive care with moderation: oxygenation without hyperoxia; ventilation without hypocarbia; avoiding extremes of blood pressure, hematocrit, blood glucose, and body temperature. Unfortunately, data from human trials are extremely limited and often poorly controlled. Furthermore, even those few existing human studies have rarely--if ever--dealt with newborns infants (Table 2). In addition, many of the existing studies do not relate to generalized asphyxia but rather to single-organ reperfusion insults. Finally, there is the critical issue of timing. Unfortunately, much of the existing experimental data relate to prophylaxis rather than treatment, severely limiting their potential for clinical applicability. Interventions may have quite different effects when administered at different phases of this most intricate process. Hyperglycemia, for example, may be neuroprotective before an insult but detrimental if induced after an asphyxial episode. Conversely, the NMDA blocker MK-801 can adversely affect outcome when given before a global asphyxial insult but can reduce seizure-related damage when given during the hyperexcitability phase. Insulin-like growth factor is also neuroprotective only when given after an insult, but it is not helpful if given before. An intimate understanding of the pathophysiologic processes involved is essential before any attempts at applying the diverse data derived from numerous animal studies to the human situation in an intelligent manner. Future studies may focus on cocktails of different mixtures of the compounds discussed or on single multipotential drugs, which would make possible a multipronged approach. However, it is essential to investigate fully the potential for toxic drug interactions, as some combinations may be produce serious consequences. For example, Gluckman and Williams evaluated the potential of combining calcium channel blockers with NMDA receptor antagonists in hypoxic-ischemic rats and found that this combination led to rapid cardiovascular collapse. Other enticing approaches for future investigations will probably include some genetic-engineering-related studies in attempt to enhance endogenous antioxidant defenses with regulon stimulation or the administration of neurotrophic growth factors. Unavoidably, the trip from the laboratory to the bedside must of necessity be an arduous and rigorous one.
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PMID:Ischemia and reperfusion injury. The ultimate pathophysiologic paradox. 977 46

The purpose of this investigation was to determine the impact of elevated partial pressures of O(2) on the steady state concentration of nitric oxide ((*)NO) in the cerebral cortex. Rodents with implanted O(2)- and (*)NO-specific microelectrodes were exposed to O(2) at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA) for up to 45 min. Elevations in (*)NO concentration occurred with all partial pressures above that of ambient air. In rats exposed to 2.8 ATA O(2) the increase was 692 +/- 73 nM (S.E., n = 5) over control. Changes were not associated with alterations in concentrations of nitric oxide synthase (NOS) enzymes. Based on studies with knock-out mice lacking genes for neuronal NOS (nNOS) or endothelial NOS (eNOS), nNOS activity contributed over 90% to total (*)NO elevation due to hyperoxia. Immunoprecipitation studies indicated that hyperoxia doubles the amount of nNOS associated with the molecular chaperone, heat shock protein 90 (Hsp90). Both (*)NO elevations and the association between nNOS and Hsp90 were inhibited in rats infused with superoxide dismutase. Elevations of (*)NO were also inhibited by treatment with the relatively specific nNOS inhibitor, 7 nitroindazole, by the ansamycin antibiotics herbimycin and geldanamycin, by the antioxidant N-acetylcysteine, by the calcium channel blocker nimodipine, and by the N-methyl-D-aspartate inhibitor, MK 801. Hyperoxia did not alter eNOS association with Hsp90, nor did it modify nNOS or eNOS associations with calmodulin, the magnitude of eNOS tyrosine phosphorylation, or nNOS phosphorylation via calmodulin kinase. Cerebral cortex blood flow, measured by laser Doppler flow probe, increased during hyperoxia and may be causally related to elevations of steady state (*)NO concentration. We conclude that hyperoxia causes an increase in (*)NO synthesis as part of a response to oxidative stress. Mechanisms for nNOS activation include augmentation in the association with Hsp90 and intracellular entry of calcium.
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PMID:Stimulation of nitric oxide synthase in cerebral cortex due to elevated partial pressures of oxygen: an oxidative stress response. 1193 51

We hypothesized that elevated partial pressures of O(2) would increase perivascular nitric oxide (*NO) synthesis. Rodents with O(2)- and.NO-specific microelectrodes implanted adjacent to the abdominal aorta were exposed to O(2) at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA). Exposures to 2.0 and 2.8 ATA O(2) stimulated neuronal (type I) NO synthase (nNOS) and significantly increased steady-state.NO concentration, but the mechanism for enzyme activation differed at each partial pressure. At both pressures, elevations in.NO concentration were inhibited by the nNOS inhibitor 7-nitroindazole and the calcium channel blocker nimodipine. Enzyme activation at 2.0 ATA O(2) appeared to be due to an altered cellular redox state. Exposure to 2.8 ATA O(2), but not 2.0 ATA O(2), increased nNOS activity by enhancing nNOS association with calmodulin, and an inhibitory effect of geldanamycin indicated that the association was facilitated by heat shock protein 90. Infusion of superoxide dismutase inhibited.NO elevation at 2.8 but not 2.0 ATA O(2). Hyperoxia increased the concentration of.NO associated with hemoglobin. These findings highlight the complexity of oxidative stress responses and may help explain some of the dose responses associated with therapeutic applications of hyperbaric oxygen.
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PMID:Stimulation of perivascular nitric oxide synthesis by oxygen. 1250 79

Pulmonary hypertension contributes significantly to morbidity and mortality in bronchopulmonary dysplasia (BPD), but little is known about the relative contribution of arterial tone, structural remodeling, and vessel density to pulmonary hypertension, especially in older patients. To determine the role of high pulmonary vascular tone in pulmonary hypertension, we studied the acute effects of oxygen tension, inhaled nitric oxide (iNO), and calcium channel blockers (CCB) in 10 patients with BPD who underwent cardiac catheterization for evaluation of pulmonary hypertension. During normoxic conditions, mean pulmonary arterial pressure (PAP) and pulmonary to systemic vascular resistance ratio (PVR/SVR) were 34 +/- 3 mm Hg and 0.42 +/- 0.07, respectively. In response to hypoxia, PAP and PVR/SVR increased by 50 +/- 8% and 82 +/- 14%, respectively (p < 0.01). Hyperoxia decreased PVR/SVR by 28 +/- 9% (p = 0.05). The addition of iNO treatment (20-40 ppm) to hyperoxia decreased PAP and PVR/SVR by 29 +/- 5% (p < 0.01) and 45 +/- 6% (p < 0.05) from baseline values, respectively, achieving near normal values. CCB did not alter PAP or PVR/SVR from baseline values. We conclude that hyperoxia plus iNO causes marked pulmonary vasodilatation in older patients with BPD, suggesting that heightened pulmonary vascular tone contributes to pulmonary vascular disease in BPD.
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PMID:Pulmonary vascular effects of inhaled nitric oxide and oxygen tension in bronchopulmonary dysplasia. 1518 2