Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

In the present study, the role of nitric oxide (NO) generated by endothelial nitric oxide synthase (NOS-3) in the control of respiration during hypoxia and hypercapnia was assessed using mutant mice deficient in NOS-3. Experiments were performed on awake and anesthetized mutant and wild-type (WT) control mice. Respiratory responses to 100, 21, and 12% O(2) and 3 and 5% CO(2)-balance O(2) were analyzed. In awake animals, respiration was monitored by body plethysmography along with O(2) consumption (VO(2)) and CO(2) production (VCO(2)). In anesthetized, spontaneously breathing mice, integrated efferent phrenic nerve activity was monitored as an index of neural respiration along with arterial blood pressure and blood gases. Under both experimental conditions, WT mice responded with greater increases in respiration during 12% O(2) than mutant mice. Respiratory responses to hyperoxic hypercapnia were comparable between both groups of mice. Arterial blood gases, changes in blood pressure, VO(2), and VCO(2) during hypoxia were comparable between both groups of mice. Respiratory responses to cyanide and brief hyperoxia were attenuated in mutant compared with WT mice, indicating reduced peripheral chemoreceptor sensitivity. cGMP levels in the brain stem during 12% O(2), taken as an index of NO production, were greater in mutant compared with WT mice. These observations demonstrate that NOS-3 mutant mice exhibit selective blunting of the respiratory responses to hypoxia but not to hypercapnia, which in part is due to reduced peripheral chemosensitivity. These results support the idea that NO generated by NOS-3 is an important physiological modulator of respiration during hypoxia.
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PMID:Blunted respiratory responses to hypoxia in mutant mice deficient in nitric oxide synthase-3. 1074 47

Nitric oxide (NO) is endogenously generated from two constitutively expressed nitric oxide synthase (NOS) isoforms, i.e., neuronal (NOS-1) and endothelial (NOS-3). Both isoforms are localized within the carotid body. Previous studies have shown endogenously generated NO modulates carotid body activity. In the present study, we examined the relative contribution of NO generated by NOS-1 and NOS-3 in respiratory reflexes arising from the carotid body. Experiments were performed on mutant mice deficient in NOS-1 or NOS-3. Wild-type (WT) mice, which contained both isoforms, served as controls. Respiration was monitored in unanesthetized mice by plethysmography. In anaesthetized mice, efferent phrenic nerve activity was monitored as index of breathing. We examined the effects of hypoxia (12% O2), cyanide and brief hyperoxia (Dejour's test) on respiration. In NOS-1 mutant mice, the ventilatory response to hypoxia (12% O2) were significantly augmented, compared to wild-type (WT) mice. By contrast, NOS-3 mutant mice displayed significantly blunted respiratory responses to hypoxia compared to WT controls. The responses to cyanide were augmented in NOS-1; whereas they were blunted in NOS-3 mutant mice. Respiratory depression in response to brief hyperoxia was more pronounced in NOS-1, while it was nearly absent in NOS-3 mutant mice. These results demonstrate that NO produced by the neuronal and endothelial NOS isoforms have different modulatory roles in carotid body chemosensitivity.
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PMID:Peripheral chemosensitivity in mutant mice deficient in nitric oxide synthase. 1084 97

Hypoxic ventilatory and phrenic responses are reduced in adult rats (3-5 months old) exposed to hyperoxia for the first month of life (hyperoxia treated). We previously reported that hypoxic phrenic responses were normal in a small sample of 14- to 15-month-old hyperoxia-treated rats, suggesting slow, spontaneous recovery. Subsequent attempts to identify the mechanism(s) underlying this spontaneous recovery of hypoxic phrenic responses led us to re-evaluate our earlier conclusion. Experiments were conducted in two groups of aged Sprague-Dawley rats (14-15 months old) which were anaesthetized, vagotomized, neuromuscularly blocked and ventilated: (1) a hyperoxia-treated group raised in 60 % O2 for the first 28 postnatal days; and (2) an age-matched control group raised in normoxia. Increases in minute phrenic activity and integrated phrenic nerve amplitude (integral Phr) during isocapnic hypoxia (arterial partial pressures of O2, 60, 50 and 40 +/- 1 mmHg) were greater in aged control (n = 15) than hyperoxia-treated rats (n = 11; P < or = 0.01). Phrenic burst frequency during hypoxia was not different between groups. To examine the central integration of carotid chemoafferent inputs, steady-state relationships between carotid sinus nerve (electrical) stimulation frequency and phrenic nerve activity were compared in aged control (n = 7) and hyperoxia-treated rats (n = 7). Minute phrenic activity, integral Phr and burst frequency were not different between groups at any stimulation frequency between 0.5 and 20 Hz. Carotid body chemoreceptor function was examined by recording whole carotid sinus nerve responses to cessation of ventilation or injection of cyanide in aged control and hyperoxia-treated rats. Electrical activity of the carotid sinus nerve did not change in five out of five hyperoxia-treated rats in response to stimuli that evoked robust increases in carotid sinus nerve activity in five out of five control rats. Estimates of carotid body volume were lower in aged hyperoxia-treated rats (4.4 (+/- 0.2) x 10(6) microm3) compared to controls (17.4 (+/- 1.6) x 10(6) microm3; P <0.01). We conclude that exposure to hyperoxia for the first month of life causes life-long impairment of carotid chemoreceptor function and, consequently, blunted phrenic responses to hypoxia.
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PMID:Life-long impairment of hypoxic phrenic responses in rats following 1 month of developmental hyperoxia. 1182 78

In this brief review the antioxidative actions of melatonin are summarized and they are discussed relative to several models of oxidative neurotoxicity. Melatonin is a ubiquitously acting antioxidant. It has been shown to scavenge the hydroxyl radical, peroxyl radical, singlet oxygen and the peroxynitrite anion; secondarily, it also scavenges the superoxide anion radical. In addition, melatonin reportedly stimulates a number of antioxidative enzymes including glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase. On the other hand, melatonin inhibits the pro-oxidative enzyme nitric oxide synthase. Besides these actions which help to resist oxidative damage, melatonin prevents membrane rigidity, reduces polymorphonuclear cell infiltration into damaged tissue, limits the adhesion of leucocytes to endothelial cells, thereby increasing blood flow and reducing edema. Some or all of these actions may have been operative in the experimental models of oxidative neurotoxicity that were improved by melatonin treatment. In brief, melatonin has been found to protect the CNS from beta-amyloid toxicity, experimental models of Parkinsonism, excitotoxicity, nitric oxide toxicity, aminolevulinic acid, lipopolysaccharide, hyperbaric hyperoxia, L-cysteine, cyanide and ischemia/reperfusion injury.
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PMID:Oxidative toxicity in models of neurodegeneration: responses to melatonin. 1267 8

The lungs of newborn rats exposed to 60% O(2) for 14 d were found to have a greatly increased cyanide-insensitive O(2) consumption, reflecting increased reactive oxygen species (ROS) formation. Exposure of the lung to hyperoxia is known to increase the production of ROS by mitochondria. We hypothesized that macrophages may also be a major contributor to this increase. Newborn rat pups were exposed to either air or 60% O(2) for 14 d and received either intraperitoneal gadolinium chloride (GdCl(3)) to abrogate macrophage influx, or inert vehicle. Lung homogenates were equilibrated in either 21% or 100% O(2) and total and cyanide-insensitive O(2) consumption, as well as nitric oxide accumulation were measured polarographically. Citrate synthase, a marker of mitochondrial mass, and nitrotyrosine, a marker of peroxynitrite formation, were quantified by Western blot. In addition to increased macrophage numbers, the lungs of 60% O(2)-exposed animals had greatly increased cyanide-insensitive O(2) consumption (p <.05 compared to air controls) and immunoreactive nitrotyrosine (p <.05), which were all completely abrogated by treatment with GdCl(3). Exposure to 60% O(2) for 14 d had no effect on peroxynitrite-independent nitric oxide release or mitochondrial mass. We conclude that increased ROS in the lungs of newborn rats exposed to 60% O(2) for 14 d was likely to be caused, in significant part, by the presence of increased numbers of macrophages.
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PMID:Macrophages as a major source of oxygen radicals in the hyperoxic newborn rat lung. 1285 76

Exposure of mammals to hyperoxia causes pulmonary and ocular pathology. Hyperoxic damage and cell death may derive from enhanced intracellular formation of reactive oxygen species (ROS), probably of mitochondrial origin. There is, however, controversy on this point. When wild-type and respiration-deficient (rho(o)) HeLa cells were cultured in 80% O2, wild-type cells stopped growing after 5 days and died thereafter whereas rho(o) cells survived and grew to confluence. This tolerance of rho(o) cells for hyperoxia was not associated with greater resistance to oxidants such as hydrogen peroxide and t-butyl hydroperoxide. Under both 20% and 80% O2, rho(o) cells exhibited substantially decreased ROS production, and, under 80% O2, rho(o) cells showed no suppression of aconitase activity or mitochondrial protein carbonyl formation. Replacement of normal mitochondria in rho(o) cells restored ROS production and susceptibility to hyperoxia. Two other approaches that diminished mitochondrial ROS generation also increased tolerance for hyperoxia. HeLa cells constantly exposed to the protonophoric uncoupler carbonyl cyanide m-chlorophenylhydrazone, which enhances respiration but decreases ROS production, showed preferential survival under 80% O2, as did HeLa cells treated with chloramphenicol, which suppresses both respiration and mitochondrial ROS production. We conclude that interactions between respiring mitochondria and O2 are primarily responsible for hyperoxic cell damage.
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PMID:Mitochondrial metabolism underlies hyperoxic cell damage. 1513 83

Paraganglia resembling the carotid body have been described in the superior laryngeal nerve (SLN) of the rat and the aim of the present study was to determine if this tissue is chemosensitive. We developed a novel isolated SLN preparation superfused with HEPES-buffered Tyrode solution at 35 degrees C in vitro. A glass suction microelectrode was used to record the electrical activity of single SLN units and a micropipette was used to pressure-eject small volumes of sodium cyanide (NaCN; 250-500 ng in 5 microl) near glomus tissue located at the main bifurcation of the SLN. The duration of the NaCN response and the number of spikes evoked after application of NaCN were compared in normoxia and hyperoxia (PO2 > 300 mmHg). Hyperoxia significantly reduced the duration and spike number of the NaCN response and a negative linear correlation existed between PO2 and response duration. In addition, hypoxia (PO2 < 60 mmHg) triggered SLN firing. Therefore, we can conclude that the paraganglia of the SLN are not only morphologically similar to the carotid body but are also excited by similar stimuli.
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PMID:Arterial chemoreceptors in the superior laryngeal nerve of the rat. 1523 64

This study examined the effect of acute hypoxic and hypercapnic cardiorespiratory stimuli, superimposed on existing cardiorespiratory disturbances in tambaqui. In their natural habitat, these fish often encounter periods of hypoxic hypercapnia that can be acutely exacerbated by water turnover. Tambaqui were exposed to periods of normoxia, hypoxia, hyperoxia and hypercapnia during which, externally oriented O2 and CO2 chemoreceptors were further stimulated, by administration into the inspired water of sodium cyanide and CO2-equilibrated water, respectively. Hyperoxic water increased the sensitivity of the NaCN-evoked increase in breathing frequency (f(R)) and decrease in heart rate. Hypoxia and hypercapnia attenuated the increase in f(R) but, aside from blood pressure, did not influence the magnitude of NaCN-evoked cardiovascular changes. Water PO2 influenced the magnitude of the CO2-evoked cardiorespiratory changes and the sensitivity of CO2-evoked changes in heart rate and blood flow. The results indicate that existing respiratory disturbances modulate cardiorespiratory responses to further respiratory challenges reflecting both changes in chemosensitivity and the capacity for further change.
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PMID:Reciprocal modulation of O2 and CO2 cardiorespiratory chemoreflexes in the tambaqui. 1576 6

Adult rats have decreased carotid body volume and reduced carotid sinus nerve, phrenic nerve, and ventilatory responses to acute hypoxic stimulation after exposure to postnatal hyperoxia (60% O2, PNH) during the first 4 weeks of life. Moreover, sustained hypoxic exposure (12%, 7 days) partially reverses functional impairment of the acute hypoxic phrenic nerve response in these rats. Similarly, 2 weeks of PNH results in the same phenomena as above except that ventilatory responses to acute hypoxia have not been measured in awake rats. Thus, we hypothesized that 2-week PNH-treated rats would also exhibit blunted chemoafferent responses to acute hypoxia, but would exhibit ventilatory acclimatization to sustained hypoxia. Rats were born into, and exposed to PNH for 2 weeks, followed by chronic room-air exposure. At 3-4 months of age, two studies were performed to assess: (1) carotid sinus nerve responses to asphyxia and sodium cyanide in anesthetized rats and (2) ventilatory and blood gas responses in awake rats before (d0), during (d1 and d7), and 1 day following (d8) sustained hypoxia. Carotid sinus nerve responses to i.v. NaCN and asphyxia (10 s) were significantly reduced in PNH-treated versus control rats; however, neither the acute hypoxic ventilatory response nor the time course or magnitude of ventilatory acclimatization differed between PNH and control rats despite similar levels of PaO2 . Although carotid body volume was reduced in PNH rats, carotid body volumes increased during sustained hypoxia in both PNH and control rats. We conclude that normal acute and chronic ventilatory responses are related to retained (though impaired) carotid body chemoafferent function combined with central neural mechanisms which may include brainstem hypoxia-sensitive neurons and/or brainstem integrative plasticity relating both central and peripheral inputs.
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PMID:Carotid sinus nerve responses and ventilatory acclimatization to hypoxia in adult rats following 2 weeks of postnatal hyperoxia. 1597 76


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