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

L-Arginine is the substrate for synthesis of nitric oxide (NO.) by NO synthase which physiologically produces vasodilation. The reaction of NO. or its metabolites with O2 or its metabolites, however, can produce toxic reactive species which may cause cellular injury. We hypothesized that excessive NO. production in isolated perfused rabbit lungs at elevated PO2 could support the production of toxic nitrogen metabolites. In isolated perfused rabbit lungs ventilated with 95% O2, 1.0 mM L-arginine caused significant pulmonary hypertension and edema. These effects of L-arginine were attenuated by the NO. synthase inhibitor, L-NAME (0.5 mM), not affected by SOD pretreatment (100 u/ml) and reversed by pretreatment with catalase (200 u/ml), suggesting a mechanism involving H2O2. This mechanism was supported by producing L-arginine mediated injury in normoxic lungs in the presence of a H2O2 generating system. This injury also was attenuated by L-NAME. On the basis of these results, we conclude that H2O2 interacts with NO. or one of its oxidized metabolites to contribute to acute lung injury during hyperoxia. Such a mechanism may involve peroxynitrite anion, although direct proof of its formation is lacking under these conditions.
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PMID:L-arginine enhances injury in the isolated rabbit lung during hyperoxia. 754 44

Nitric oxide (NO) production is involved in the development of oxygen toxicity of the central nervous system (CNS) since inhibition of nitric oxide synthase (NOS) significantly protects animals from hyperbaric oxygen (HBO)-mediated convulsions. One potential mechanism for this protection is that NOS inhibition decreases cerebral O2 delivery thereby limiting the PO2 of brain tissues during hyperoxia. To investigate this hypothesis, anesthetized rats were exposed to 7, 100, and 7% O2 under 3 atm abs for 15-min periods. Cortical blood flow (CBF) and O2 tension were measured with a laser-Doppler flowprobe and an O2 electrode, respectively, with and without pretreatment with the NOS doppler, N omega-nitro-L-arginine methyl ester (L-NAME). We found that HBO exposure significantly increased the brain O2 tension whereas changes in CBF were not significant. Compared with control rats, L-NAME administration did not change either brain O2 tension or CBF during the period of the experiment. We conclude that the effects of L-NAME on cortical oxygenation and CBF during HBO exposure in rats do not seem to provide a physiologic explanation for protection from CNS O2 toxicity by the drug.
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PMID:Inhibition of nitric oxide synthase on brain oxygenation in anesthetized rats exposed to hyperbaric oxygen. 857 25

We tested the hypothesis that hyperoxia does not cause adequate constriction of choroidal vessels of the newborn (1 to 5 days old) pig, resulting in increased O2 delivery to the retina, possibly due to excess production and/or effects of vasodilators such as nitric oxide (NO). Hyperoxia (100% O2, 45 minutes) led to a decrease in retinal blood flow (RBF) of both newborn and juvenile (5 to 6 weeks old) pigs and also reduced choroidal blood flow (ChBF) in juvenile but not in newborn pigs; the absence of hyperoxia-induced ChBF response in the newborn was associated with a rise in choroidal O2 delivery. Ibuprofen (prostaglandin G/H synthase inhibitor) and 1,3-dimethyl-2-thiourea (a free radical scavenger) did not modify the choroidal hemodynamic responses to hyperoxia in newborn pigs. However, in newborn animals treated with the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME), hyperoxia caused a decrease in blood flow and O2 delivery to the choroid. Consistent with these effects of L-NAME, hyperoxia induced an increase in choroidal cGMP in newborn pigs ventilated with 100% O2 and stimulated nitrite production in isolated choroids exposed to hyperoxia from newborn but not juvenile pigs; these effects were inhibited by NOS blockers. Also, both constitutive and inducible NOS activities were higher in choroidal tissues from newborn than from juvenile animals. In addition, the vasorelaxant effect of the NO donor sodium nitroprusside in vitro was also greater on choroids from newborn than from juvenile pigs. Finally, L-NAME prevented the hyperoxia-induced increase in peroxidation products in the choroid of newborns. It is concluded that hyperoxia does not lead to a decrease in blood flow and O2 delivery to the choroid of the newborn because of increased NO synthesis and effects; since the choroid is the main source of O2 supply to the retina, the present data contribute in providing an explanation for the increased susceptibility of the immature neonate to hyperoxia-induced retinopathy.
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PMID:Increased nitric oxide synthesis and action preclude choroidal vasoconstriction to hyperoxia in newborn pigs. 878 83

Exposure to high oxygen concentration leads to acute lung injury and death in rats after 72 h. The pathophysiology of this phenomenon relies on several mechanisms, including alteration of vascular reactivity, recruitment and activation of neutrophils and alveolar macrophages, production of cytokines and excess production of free radicals. In addition to its potent vasodilating effect, nitric oxide (NO) has also been reported to prevent free radical-mediated damage. We wanted to determine whether NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, might modulate oxygen toxicity. In rats exposed to continuous high oxygen concentration, we studied the effect of administration of 50 mg.kg-1 of intraperitoneal L-NAME twice a day on the first day of oxygen exposure. L-NAME resulted in earlier death, since 57% of the animals exposed to oxygen and injected with L-NAME died within 60 h as compared to 22% of the animals exposed to oxygen and treated with saline (p < 0.01). Haematocrit and bronchoalveolar lavage fluid protein were also significantly increased in animals exposed to oxygen and receiving L-NAME. The lung water content was higher in the oxygen-exposed groups (p < 0.01) and slightly decreased by L-NAME (p < 0.05). Thiobarbituaric acid reactive substances (TBARS) were elevated in plasma (p < 0.01) and decreased in lung (p < 0.001) of oxygen-exposed animals, but no significant effect of L-NAME was observed. NG-nitro-L-arginine methyl ester had a deleterious effect in rats exposed to hyperoxia, which might suggest that endogenous nitric oxide has a protective role against hyperoxia-induced pulmonary lesions.
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PMID:L-NAME aggravates pulmonary oxygen toxicity in rats. 898 Sep 65

Vascular tone has been shown to be importantly influenced by flow-induced release of endothelium-derived vasodilators. The purpose of the present study was to test the hypothesis that in porcine coronary resistance-size arterioles, flow-induced vasodilation is sensitive to oxygen tension. Arterioles (55-150 mu m) were studied in vitro under conditions of constant intraluminal pressure to dynamically measure arteriolar diameter in response to changes in flow or, alternatively, in response to bradykinin under three conditions: hyperoxia (pO(2) 400 mm Hg), normoxia (pO(2) 160 mm Hg), and hypoxia (p0(2) 40 mm Hg). Under conditions of constant pressure and no flow, hypoxia alone resulted in vasodilation that was blocked by the nitric oxide synthase inhibitor omega-nitro-L-arginine methyl ester (L-NAME). Hypoxia did not alter the vasodilator response to bradykinin when compared to the vasodilator response to bradykinin during normoxia. During hyperoxia, flow-induced vasodilation was significantly reduced by either indomethacin, or L-NAME. Indomethacin and L-NAME combined completely abolished flow-induced vasodilation under conditions of hyperoxia. Under conditions of normoxia and hypoxia, indomethacin or L-NAME alone only partially blocked flow-induced vasodilation. No further inhibition was observed when indomethacin and L-NAME were combined. Glybenclamide failed to alter flow-induced vasodilation either alone or in combination with indomethacin and L-NAME. The results suggest that the mechanisms responsible for flow-induced vasodilation in coronary arterioles are complex and are different depending upon the oxygen tension. During hyperoxia, vasodilation is due to the combined actions of prostanoids and nitric oxide, while under conditions of normoxia and hypoxia, flow-induced vasodilation is the result of not only prostanoids and nitric oxide, but of another as of yet unidentified oxygen-sensitive endogenous vasodilator.
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PMID:Effects of oxygen tension on flow-induced vasodilation in porcine coronary resistance arterioles. 899 34

Nitric oxide (NO) may either protect against or contribute to oxidant-induced lung injury. In this study, we sought to determine whether either inhaled NO in concentration of 10 and 100 parts per million (ppm) or inhibition of endogenous NO formation with L-NG nitroarginine methyl ester (L-NAME) or aminoguanidine alters the extent of lung injury in rats breathing 100% O2. Lung thiobarbituric acid reactive substances (TBARS), wet to dry lung weight ratio (Q(W)/Q(D)), vascular and epithelial permeability (assessed by simultaneous intravenous administration of 131I-labeled albumin and intraalveolar instillation of 125I-labeled albumin), alveolar liquid clearance (evaluated based on the increase in alveolar protein concentration), and lung liquid clearance (gravimetric method) were determined after 40 h exposure to either 100% or 21% O2. Exposure to hyperoxia caused increases in lung TBARS from 10.5 +/- 0.7 to 13.7 +/- 1.5 micromol/mg protein (p < 0.05); in blood hemoglobin concentration (Hb) from 14 +/- 1 g/dl to 17 +/- 1 g/dl (p < 0.05); in the Q(W)/Q(D) ratio from 4.02 +/- 0.3 to 5.31 +/- 0.5 (p < 0.05); and in alveolar-arterial oxygen tension difference from 124 +/- 14 mm Hg to 241 +/- 61 mm Hg (p < 0.05); as well as a decrease in blood pressure, from 131 +/- 15 mm Hg to 72 +/- 26 mm Hg (p < 0.05). Hyperoxia also increased vascular albumin leakage and moderately altered epithelial barrier permeability to protein. Inhalation of 10 ppm NO prevented the increases in TBARS and Q(W)/Q(D), had no effect on the alveolar barrier impermeability to protein, and improved alveolar liquid clearance. Inhalation of 100 ppm NO did not alter the increases in TBARS and Q(W)/Q(D) but increased vascular permeability to protein. Survival of rats exposed to hyperoxia was not improved by inhaled NO. Treatment with L-NAME or aminoguanidine reduced survival. L-NAME, but not aminoguanidine, increased lung TBARs. These results suggest that, depending on its concentration, inhaled NO can either reduce or increase the early consequences of hyperoxic lung injury. Treatment with L-NAME, and to a lesser extent aminoguanidine, worsened hyperoxic lung injury, indicating a protective effect of endogenous NO.
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PMID:Effects of inhaled nitric oxide or inhibition of endogenous nitric oxide formation on hyperoxic lung injury. 919 2

The involvement of the L-arginine-nitric oxide (NO) pathway in the pathogenesis of hyperoxia-induced seizures was studied by using agents controlling NO levels. We selected two inhibitors of nitric oxide synthase, the systemic inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) and the novel cerebral-specific inhibitor 7-nitroindazole, and two generators of NO, the NO donor S-nitroso-N-acetylpenicillamine and the physiological precursor L-arginine. Rats with chronic cortical electrodes were injected intraperitoneally with different doses of one of the agents or their vehicles before exposure to 0.5 MPa O2 and O2 with 5% CO2 at an absolute pressure of 0.5 MPa. The duration of the latent period until the onset of electrical discharges in the electroencephalogram was used as an index of central nervous system O2 toxicity. The two nitric oxide synthase inhibitors L-NAME and 7-nitroindazole significantly prolonged the latent period to the onset of seizures on exposure to both hyperbaric O2 and to the hypercapnic-hyperoxic mixture. Pretreatment with the NO donor S-nitroso-N-acetylpenicillamine significantly shortened the latent period, whereas L-arginine, the physiological precursor of NO, significantly prolonged the latent period to onset of seizures. Our results suggest that the L-arginine-NO pathway is involved in the pathophysiology of hyperoxia-induced seizures via various regulating mechanisms.
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PMID:L-arginine-NO pathway and CNS oxygen toxicity. 957 10

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

To assess the effects of exposure of the lung to hyperoxic conditions on reactivity of pulmonary microcirculation to hypoxic stimulation, we measured hypoxia-elicited overall pulmonary pressor changes (HPV) and microvascular diameter changes in intraacinar arterioles, venules, and capillaries in isolated perfused rat lungs exposed to a hyperoxic environment (90% O2). To estimate the importance of vasoactive prostaglandins and nitric oxide (NO) for HPV modification, we examined the roles of constitutive and inducible forms of cyclooxygenase (COX-1 and COX-2) and those of NO synthase (eNOS and iNOS). Indomethacin was used for inhibiting both COX-1 and COX-2, while NS-398 was used as a selective inhibitor of COX-2. Both eNOS and iNOS were suppressed by L-NAME, whereas iNOS alone was inhibited by aminoguanidine. Microvascular diameter was measured with a real-time confocal laser scanning luminescence microscope. We found that (1) exposure to hyperoxia caused overall HPV and arteriolar constriction to be attenuated; (2) the blunted HPV was restored by L-NAME but not by aminoguanidine, indomethacin, or NS-398; and (3) arteriolar constriction was improved by either L-NAME, aminoguanidine, or indomethacin but only slightly by NS-398. In conclusion, attenuation of overall HPV in hyperoxia-exposed lungs is explicable mainly by excessive NO generated via eNOS, while impaired arteriolar constriction is caused by NO yielded by eNOS and iNOS as well as by vasodilating prostaglandin(s) produced by COX-1.
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PMID:Impaired hypoxic vasoconstriction in intraacinar microvasculature in hyperoxia-exposed rat lungs. 970 Jan 41

The interaction between constitutive nitric oxide and oxygen may depend on the degree of tissue oxygenation and may play a critical role in the pathophysiological response to endotoxaemia. We investigated if hyperoxia (100% O2) attenuated the systemic and pulmonary vasoconstriction and increased biosynthesis of thromboxane B2 (TXB2) and 6-keto-prostaglandin (PG) F1alpha induced by inhibition of nitric oxide synthase with NG-nitro-L-arginine-methyl-ester (L-NAME) in a porcine model of endotoxaemia. Twenty-two domestic, random source pigs, weighing 15.4 +/- 2.7 kg (mean +/- standard deviation) were the subjects of this study. Pigs were anaesthetized with isoflurane in 100% O2, orotracheally intubated and ventilated to maintain normocapnia, and then instrumented for haemodynamic monitoring. Following instrumentation, pigs were maintained at an end-tidal isoflurane concentration of 2%. Pigs were randomly assigned to treatment groups: saline + 30% O2 (Control, n = 6); Escherichia coli lipopolysaccharide (5 microg/kg/h from 1 to 2 h followed by 2 microg/kg/h from 2 to 5 h) + 30% O2 (LPS, n = 4); L-NAME (0.5 mg/kg/h, from 0 to 5 h) + LPS + 100% O2 (n = 6); and L-NAME + LPS + 30% O2 (n = 6). L-NAME and endotoxin significantly (P < 0.05) increased mean arterial pressure, mean pulmonary arterial pressure, and systemic and pulmonary vascular resistance index beginning at 90 min. When results were pooled across all time periods, mean arterial pressure and mean pulmonary arterial pressure were significantly higher in the L-NAME + LPS + 30% O2 group than all other groups, reflecting pulmonary and systemic vasoconstriction. Hyperoxia attenuated the L-NAME + LPS-induced increases in TXB2 and 6-keto-PGF1alpha concentrations at 90 and 120 min and 120 min, respectively, although the differences were not statistically significant. These results support the observation that nitric oxide synthase inhibition with L-NAME has deleterious haemodynamic effects in this model of endotoxaemia. The temporal attenuation of L-NAME-induced pulmonary and systemic vasoconstriction by hyperoxia suggested that the haemodynamic effects of acute endotoxaemia were in part influenced by the relative amounts of nitric oxide and oxygen present.
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PMID:The effects of hyperoxia on the biosynthesis of cyclooxygenase products and haemodynamic response to nitric oxide synthase inhibition with L-NAME in endotoxaemic pigs. 981 34


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