UMLS:C0406810 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) was measured directly after spinal cord injury (SCI) in rats by an ESR spin-trapping technique using Fe2+ and diethyldithiocarbamate (DETC). The levels of NO and lipid peroxides expressed as thiobarbituric acid reactive substances (TBARS) were increased by SCI in the injured region and the adjacent central region. Pretreatment with 30 mg/kg of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of NO synthase, accelerated increases of the TBARS level and myeloperoxidase (MPO) activity in the injured tissue and caused deterioration of hind limb motor function after SCI, suggesting that NO formation by constitutive NO synthase (c-NOS) has a protective effect against cellular damage resulting from ischemia-reperfusion after SCI. Though c-NOS mRNA expression was not altered after SCI, inducible NO synthase (i-NOS) mRNA expression increased to a maximum of 24 h after SCI with progress of motor dysfunction. Intravenous injection of L-NAME (0.1 mg/kg) 6, 24, 48, and 72 h after SCI reduced the motor disturbance. These results indicate that NO induced by i-NOS may be neurotoxic in the subacute phase after SCI.
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PMID:Roles of nitric oxide in compression injury of rat spinal cord. 890 74

The aim of this study was to elucidate whether nitric oxide (NO) is involved in re-innervation of rat molar tooth pulp following transection of the inferior alveolar nerve. The inferior alveolar nerves (IAN) of rats were transected unilaterally under anesthesia with chloral hydrate. The animals received horseradish peroxidase (HRP) application to mandibular molar tooth pulps on both sides and were fixed by transvascular perfusion. The average number of labeled cells on each side of the trigeminal ganglion was not significantly different [101 +/- 11 (mean +/- S.E.M.; n = 6, left) and 89 +/- 11 (n = 6, right)]. With HRP application on postoperative day 3, the ratio of the number of labeled neurons in the transected vs. non-transected (contralateral) sides was 31.5 +/- 5.8% (n = 11). The i.p. administration of N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg, once a day for a period of 4 days), but not D-NAME, significantly decreased the ratio of the number of labeled neurons (10.1 +/- 7.0%, n = 10). L-Arginine (300 mg/kg, i.p., once a day for a period of 4 days) slightly increased the number of labeled neurons on the transected side. Clonidine (25 microg/kg, i.p., once a day for a period of 4 days) failed to exhibit any significant effect on nerve regeneration. In the trigeminal ganglion ipsilateral to the transected IAN on postoperative day 4, NADPH-diaphorase (NADPH-d)-positive neurons had significantly increased. On the other hand, no changes in NADPH-d were observed in the superficial layers of the subnucleus caudalis of the spinal trigeminal nucleus from where primary neurons innervating the mammalian tooth pulp project. These results suggest that NO is involved in several mechanisms related to neuronal regeneration.
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PMID:Involvement of nitric oxide in re-innvervation of rat molar tooth pulp following transection of the inferior alveolar nerve. 920 Apr 96

Nitric oxide (NO) synthase inhibitors, such as NG-nitro-L-arginine methyl ester (L-NAME), have been shown to attenuate endotoxin-induced uveitis (EIU) but they could increase leukocyte adhesion to the vascular endothelium. We hypothesize that a concomitant treatment with the 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) in 50% dimethylsulfoxide (DMSO, a hydroxyl radical scavenger) could improve the anti-inflammatory activity of L-NAME. EIU was induced in albino rabbits by intravitreal injection of 100 ng lipopolysaccharide. Animals were treated with multiple intraperitoneal injections of 50% DMSO in phosphate-buffered saline (PBS), NDGA (10 mg/kg) in 50% DMSO, L-NAME (50 mg/ kg) in PBS, or the combination NDGA+L-NAME. Uveitis was assessed by slit lamp examination, protein levels in aqueous humor, and myeloperoxidase (MPO) activity in the iris/ciliary body 6 h after induction. Nitrite, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), platelet-activating factor (PAF) and interleukin-1 beta (IL-1 beta) levels in aqueous humor were also determined. NDGA or L-NAME alone did not show a significant reduction of uveitis intensity, although a significant decrease in MPO or in proteins was found, respectively. The combination NDGA+L-NAME significantly reduced the uveitis intensity, MPO in the iris/ciliary body, and the levels of nitrites, LTB4, PGE2, and PAF in aqueous humor. IL-1 beta levels were lower than the detection limit of the radioimmunoassay in all treatment groups. We conclude that concomitant treatment with NDGA in DMSO improves the anti-inflammatory activity of L-NAME during the early phase of EIU, suggesting that the inhibition of NO synthesis could enhance leukocyte infiltration and the release of oxygen free radicals.
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PMID:Concomitant treatment with a 5-lipoxygenase inhibitor improves the anti-inflammatory effect of the inhibition of nitric oxide synthase during the early phase of endotoxin-induced uveitis in the rabbit. 926 46

The present investigation was undertaken to study the alterations in free radical generation and release of nitric oxide (NO) from polymorphonuclear leukocytes (PMNLs) following thrombosis. Thrombosis was induced in rats by intravenous injection of collagen and adrenaline. PMNLs were separated from rat blood by using dextran sedimentation and Ficoll-Hypaque. Arachidonic acid (AA), formyl methionine leucine phenylalanine (FMLP) and opsonized zymosan (OZ) induced free radical generation was estimated as luminol (LCL) and Lucigenin (LUCDCL) dependent chemiluminescence. PMNLs nitric oxide synthase (NOS) activity and NO release were measured by using [14C] L-Arginine (L-Arg) and oxy-hemoglobin respectively. LCL and LUCDCL responses in rat PMNLs were significantly attenuated following thrombosis. There was no change in the release of myeloperoxidase enzyme (MPO) from PMNLs obtained following thrombosis. PMNLs NOS activity and NO release were also found to be increased after thrombosis. Pretreatment of rat PMNLs with 10 mM L-NAME (NO precursor) or 100 microM sodium nitroprusside (NO donor), resulted in significant reduction of AA induced LCL response. Results obtained indicate that NO release form PMNLs was augmented while free radical generation response was attenuated after the induction of thrombosis.
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PMID:Alterations in the free radical generation and nitric oxide release from rat peripheral polymorphonuclear leukocytes following thrombosis. 926 95

The time-dependent actions following pretreatment or delayed administration of the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on colonic inflammation and inducible NO synthase activity following the intrarectal administration of trinitrobenzene sulphonic acid (TNBS) were evaluated in the rat. Intracolonic instillation of TNBS (30 mg in 0.25 ml of 50% ethanol) led to macroscopic injury, an increase of mucosal myeloperoxidase activity and the expression of the Ca2+-independent inducible NO synthase over 8 days. The inflammatory response following TNBS reached maximum levels between 12 and 72 h and then it declined until 14 days. Oral administration of L-NAME (25 mg/kg per 24 h in the drinking water) 2 days before TNBS augmented macroscopic damage and increased colonic inducible NO synthase activity 6, 12, 24 and 72 h after TNBS administration. In contrast, when L-NAME was administered 6 h after TNBS instillation, at time of expression of inducible NO synthase, the macroscopic lesions were reduced, as well as the enhanced inducible NO synthase activity, determined, over 72 h. Delayed (6 h after TNBS) administration of L-NAME also attenuated the colonic myeloperoxidase activity provoked by TNBS, after 24 h. This activity was not affected by pretreatment (2 days before TNBS) with L-NAME. These findings indicate that the timing of administration of non-selective NO synthase inhibitors such as L-NAME, in models of colitis is critical to the eventual outcome. Thus, pretreatment with L-NAME, which will inhibit constitutive NO synthase, exacerbates the subsequent damage following challenge. In contrast, delayed administration of L-NAME at the time of inducible NO synthase expression, has a beneficial action on the colonic injury and inflammation.
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PMID:Time-dependent actions of nitric oxide synthase inhibition on colonic inflammation induced by trinitrobenzene sulphonic acid in rats. 938 36

We examined the effects of various nitric oxide synthase (NOS) inhibitors on development of gastric lesions induced by compound 48/80 (48/80) in rats and investigated the roles of NO and inducible NOS (iNOS) in inflammatory gastric responses. Animals were given 48/80 (1 mg/kg, i.p.) once daily for 4 days, and the stomachs were examined for lesions 24 h after the final administration. NOS inhibitors such as L-NAME, L-NMMA, aminoguanidine or dexamethasone were administered for 4 days during 48/80 treatment. The repeated administration of 48/80 caused damage in the stomach with severe edema in the submucosa. These lesions induced by 48/80 were dose-dependently prevented by concurrent administration of L-NAME. The protective effect of L-NAME on 48/80-induced gastric lesions was mimicked by L-NMMA, aminoguanidine as well as dexamethasone, and significantly antagonized by co-administration of L-arginine but not by D-arginine. Acid secretion was slightly decreased after 48/80 treatment, but was significantly augmented by the combined administration of L-NAME with 48/80. The mucosal MPO activity, TBA reactants and vascular permeability in the stomach were all increased after 48/80 treatment, but these changes were also significantly mitigated by co-administration of L-NAME. The Ca(2+)-independent NOS activity in the mucosa was increased four times during 48/80 treatment, and this change was also inhibited by dexamethasone. These results suggest that: 1) the repeated administration of 48/80 induced inflammatory gastric lesions in the rat stomach; 2) the pathogenic mechanism of these lesions involves endogenous NO produced by iNOS, in addition to oxyradical formation; and 3) the deleterious role of NO during 48/80 treatment may be accounted for by a cytotoxic action of peroxynitrite, which is formed in the presence of NO and superoxide radicals.
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PMID:Role of nitric oxide in pathogenesis of gastric mucosal damage induced by compound 48/80 in rats. 940 87

Hemorrhagic shock results in hepatocellular dysfunction and hepatic injury that may contribute to the development of liver failure and multiple organ dysfunction in trauma patients. The specific mediators involved in this process remain incompletely defined. We have previously demonstrated that inhibition of nitric oxide (NO) synthesis in a rat model of moderately severe hemorrhagic shock increases hepatic injury, suggesting that NO synthesis is beneficial after hemorrhage. To further define the role of NO in hepatic function during hemorrhagic shock, rats were subjected to a severe hemorrhagic shock insult in which they were bled to a mean arterial pressure of 40 mmHg until 40% of their shed blood had been returned and then were resuscitated. Rats were treated with the NO synthase inhibitor L-nitroarginine methyl ester (L-NAME) or the NO donor S-nitroso-N-acetylpenicillamine beginning either during the hypotensive period or after resuscitation. When instituted during the hypotensive period, low dose L-NAME infusion significantly increased hepatic injury. When L-NAME was infused after resuscitation, no increase in hepatic injury was detected even when the L-NAME dose was increased by a factor of four. The increased hepatic injury produced by L-NAME was associated with increased myeloperoxidase content in the lung, suggesting that L-NAME led to a greater accumulation of neutrophils during shock. Administration of the NO donor S-nitroso-N-acetylpenicillamine reduced hepatocellular enzyme release. Our results suggest that ongoing NO synthesis during the hypotensive phase of hemorrhagic shock is essential in preventing shock-induced hepatic injury and this may be due, in part, to the interaction between NO and circulating neutrophils.
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PMID:Inhibition of nitric oxide synthesis during severe shock but not after resuscitation increases hepatic injury and neutrophil accumulation in hemorrhaged rats. 942 54

The objective of this study was to determine the effects that certain nitric oxide synthase inhibitors have on the spontaneous intestinal and colonic inflammation that develops in HLA-B27 transgenic rats and compare these data to those obtained using sulfasalazine (SZ). In an attempt to more closely mimic the clinical situation, drug treatment was begun after the onset of colitis. HLA-B27 male rats that developed clinical signs of colitis (diarrhea/loose stools) at 17 wk of age were randomized into fours groups consisting of one untreated colitic group and three treatment groups that received either aminoguanidine (AG; 52 micromol/kg/day), NG-nitro-L-arginine methyl ester (L-NAME; 45 micromol/kg/day) or SZ (130 mg/kg/day) in their drinking water for 14 days. Aged-matched Fisher 344 male rats were used as healthy controls. After 3 wk of treatment, ileal and colonic mucosal permeabilities, granulocyte infiltration and nitric oxide were quantified using blood-to-lumen clearance of 51Cr-EDTA, tissue myeloperoxidase activity, and plasma levels of nitrate and nitrite, respectively. We found that both AG and L-NAME but not SZ significantly attenuated the increases in plasma nitrate and nitrite levels. Interestingly, all three drugs were effective at significantly attenuating the increases in myeloperoxidase activity in the distal colon. Treatment with AG and SZ but not L-NAME were effective at significantly attenuating the increase in ileal and colonic permeabilities. Quantitative histological analysis revealed that AG and L-NAME but not SZ significantly attenuated the increase in the mucosal thickness and crypt depth in the distal colon compared to untreated colitis. Taken together, these data demonstrate that oral administration of certain nitric oxide synthase inhibitors or SZ to animals with active colitis attenuates the colonic inflammation by at least two different mechanisms. One mechanism appears to be dependent on inhibition of NO production whereas the other mechanism does not.
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PMID:Effects of nitric oxide synthase inhibition or sulfasalazine on the spontaneous colitis observed in HLA-B27 transgenic rats. 945 20

We investigated the contribution of eicosanoids, platelet-activating factor, tumor necrosis factor and nitric oxide to the neutrophil influx and development of pulmonary haemorrhagic lesions following immune-complex-induced pneumonitis in rats and possible interactions between these mediators. Increased levels of leukotriene B4 and tumor necrosis factor, measured by enzyme immunoassay and L-929 cytotoxicity assay, were found in the bronchoalveolar lavage 1 and 4 h after induction of the reaction, respectively, and their release was dependent on the previous generation of platelet activating factor. Antagonism of leukotriene B4 receptors by RO-0254094 (2-[(5-carboxypentyl])oxy]-6-[6-[3,4-dihydro-4-oxo-8-propyl-2H-1-benzopy ran-7-yl)oxy]hexyl] benzenepropanoic acid), inhibition of nitric oxide synthesis by L-NAME (Nw-nitro-L-arginine methyl ester) and antagonism of PAF-receptors by WEB-2170 (5-(2-chlorphenyl)-3-4-dihydro-10-methyl-3-((4-morpholinyl)carbony l)-2 H,7H-cyclopenta (4,5)thieno(3,2-f)(1,2,4)-triazolo-4,3,a)91,4)diazepine), significantly inhibited the intensity of haemorrhage, evaluated by the increased levels of extravascular hemoglobin in homogenates of lung tissues. Little evidence support the role of tumor necrosis factor in these lesions. The infiltration of neutrophils, evaluated by measuring myeloperoxidase in homogenates of lungs, was reduced by compounds L-663,536 (3-[1-(4 chlorobenzyl)-3-t-butyl thio-5-isopropylindol-2-yl]-2-2-dimethylpropanoic acid), WEB-2170 and L-NAME. These results indicate that neutrophil infiltration and haemorrhagic lesions in immune-complex-induced lung inflammation are mediated by platelet activating factor, leukotriene B4 and nitric oxide and point out to interesting interactions between these mediators.
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PMID:Lipid mediators, tumor necrosis factor and nitric oxide and their interactions in immune-complex-induced lung injury. 980 71

Nitric oxide is a radical with vasodilating properties that protects tissues from neutrophil-mediated ischemia-reperfusion injury in the heart and intestine. Previous studies in our laboratory suggested that L-arginine, a nitric oxide precursor, can protect skin flaps from ischemia-reperfusion injury. In this study, we examined the effects of L-arginine on the survival of myocutaneous flaps in a large animal model and established whether this effect was mediated by nitric oxide and neutrophils. Two superiorly based 15 x 7.5 cm epigastric myocutaneous island flaps were dissected in 15 Yorkshire pigs weighing 45 to 50 kg. One of the flaps was subjected to 6 hours of arterial ischemia and then reperfused for 4 hours (ischemia-reperfusion flaps), whereas the other flap was used as a non-ischemic control (non-ischemia-reperfusion flaps). The flaps were divided into four groups: control non-ischemia-reperfusion flaps that received only saline (group I); ischemia-reperfusion flaps that were treated with saline (group II); and flaps treated with either L-arginine (group III) or Nomega-nitro-L-arginine methylester (L-NAME), a nitric oxide synthase competitive inhibitor, plus L-arginine in equimolar amounts (group IV). These drugs were administered as an intravenous bolus 10 minutes before the onset of reperfusion, followed by a 1-hour continuous intravenous infusion. Full-thickness muscle biopsies were taken at baseline, 3 and 6 hours of ischemia, and 1 and 4 hours of reperfusion. The biopsies were evaluated by counting neutrophils and measuring myelo-peroxidase activity. At the end of the experiment, skeletal muscle necrosis was quantified using the nitroblue tetrazolium staining technique, and a full-thickness biopsy of each flap was used for determination of water content. Statistical analysis was performed using analysis of variance and the Newman-Keuls test. Non-ischemia-reperfusion flaps showed no muscle necrosis. Ischemia-reperfusion flaps treated with saline had 68.7 +/- 9.1 percent necrosis, which was reduced to 21.9 +/- 13.6 percent with L-arginine (p < 0.05). L-NAME administered concomitantly with L-arginine demonstrated a necrosis rate similar to that of saline-treated ischemia-reperfusion flaps (61.0 +/- 17.6 percent). Neutrophil counts and myeloperoxidase activity after 4 hours of reperfusion were significantly higher in ischemia-reperfusion flaps treated with L-NAME and L-arginine as compared with the other three groups (p < 0.05). Flap water content increased significantly in ischemia-reperfusion flaps treated with saline and L-NAME plus L-arginine versus non-ischemia-reperfusion flaps (p < 0.02) and L-arginine-treated ischemia-reperfusion flaps (p < 0.05). There was no difference in flap water content between ischemia-reperfusion flaps treated with L-arginine and non-ischemia-reperfusion flaps. Administration of L-arginine before and during the initial hour of reperfusion significantly reduced the extent of flap necrosis, neutrophil accumulation, and edema due to ischemia-reperfusion injury in a large animal model. This protective effect is completely negated by the use of the nitric oxide synthase blocker L-NAME. The mechanism of action seems to be related to nitric oxide-mediated suppression of ischemia-reperfusion injury through neutrophil activity inhibition.
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PMID:Use of a nitric oxide precursor to protect pig myocutaneous flaps from ischemia-reperfusion injury. 981 Oct 2

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