UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We sought to clarify the role of nitric oxide (NO) generated from inducible NO synthase (iNOS) during healing of rat gastric ulcers. After gastric ulcers were induced by acetic acid, rats were treated with vehicle, N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), and dexamethasone (Dex) by gastric intubation twice a day for 3 days to 1 week. L-NAME significantly delayed healing compared with vehicle. AG and Dex significantly reduced ulcer size 3 days after ulcer induction but did not further reduce ulcer size 1 week after induction. iNOS expression was present in inflammatory cells, some epithelial cells, and in vascular smooth muscle in the regenerating mucosa of the vehicle-treated group. However, the number of iNOS-positive inflammatory cells increased in the AG- and L-NAME-treated groups. AG and L-NAME significantly increased the number of inflammatory cells with endogenous peroxidase and significantly reduced the number of apoptotic inflammatory cells compared with vehicle. In conclusion, inhibition of iNOS increases the number of inflammatory cells in the ulcer margin and delays ulcer healing. These observations suggest that NO generated from iNOS not only participates in ulcer formation but also plays a beneficial role in ulcer healing, in part by the exclusion of iNOS-positive inflammatory cells from the regenerating mucosa.
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PMID:Inhibition of inducible nitric oxide synthase delays gastric ulcer healing in the rat. 987

Changes in gastric emptying and orocaecal transit time in patients with ulcerative colitis suggest that disturbances in gut motility may not be restricted to inflamed sites. This study sought to characterize changes in the motility of noninflamed ileum in a rat colitis model and to explore the mechanism(s) potentially involved. The myoelectrical activity of the ileum was recorded in rats with trinitrobenzene sulphonic acid (TNBS)-induced colitis. The degree of ileal and colonic inflammation was assessed by quantification of macroscopic damage and myeloperoxidase activity (MPO). The effect on ileal motility of pretreatment with atropine, indomethacin and NG-nitro-L-arginine-methyl ester (L-NAME) was investigated. TNBS-induced inflammation was restricted to the distal colon, as evidenced by morphological scores and MPO. Colitis was associated with increased frequency of ileal migrating motor complexes, characterized mainly by a decrease in the duration of phases I and III. The occurrence of ileal giant migrating complexes remained unchanged. The myoelectrical changes observed in the ileum persisted after treatment with atropine, indomethacin and L-NAME. Distal colitis is associated with abnormal myoelectrical activity in the noninflamed ileum of rats. Neither acetylcholine nor prostaglandins and nitric oxide seem to be involved.
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PMID:Altered myoelectrical activity in noninflamed ileum of rats with colitis induced by trinitrobenzene sulphonic acid. 1008 35

Nitrite (NO2-), an end product of nitrogen radical metabolism, has recently been shown to increase tyrosine nitration by activated leukocytes indicating that nitrite modulates the immune response. We investigated the hypothesis that nitrite may increase nitration of molecular targets within activated cells leading to altered cell cycle progression. Intracellular nitrite was increased by transfection of murine macrophage-like RAW 264.7 cells with the nitrate reductase gene obtained from barley. Nitrate reductase facilitates the conversion of nitrate to nitrite; thus when extracellular nitrate is present, intracellular nitrite will be increased. Results show that addition of KNO3 increases NO2- production and intracellular nitrotyrosine accumulation in the transfectant but not the parent. Inhibition of nitric oxide synthesis with L-NAME during activation with IFN-gamma + LPS reduced NO2- production to the same extent in both cell lines; however, cellular accumulation of nitrotyrosine was reduced by only 25% in the transfectant (P = 0.21) and 49% in the parent cell line (P = 0.007), suggesting that intracellular nitrite increased nitrotyrosine accumulation through a pathway not requiring NO synthesis, i.e., myeloperoxidase system. Approximately 15% of the transfected cells had 4n DNA content 24 h postactivation compared to < 1% of the parent cells. Increased DNA copy number was correlated to nitrotyrosine accumulation. These findings show that intracellular nitrite can increase accumulation of nitrotyrosine and that nitration is linked to cell cycle perturbation.
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PMID:Nitrate reductase alters 3-nitrotyrosine accumulation and cell cycle progression in LPS + IFN-gamma-stimulated RAW 264.7 cells. 1010 Apr 92

The present study was undertaken to explore the role of nitric oxide (NO) in the pathogenesis of experimental non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy. We assessed the role of NO inhibition and donation in indomethacin-induced gastric mucosal dysfunction. The stomach was perfused with vehicle (control) for 20 min, followed by indomethacin (10 mg ml-1 in 1 25 % sodium bicarbonate, pH 8 4) for 120 min. NG-nitro-L-arginine methyl ester (L-NAME, 5 and 10 mg kg-1, I.V. bolus), L-arginine, D-arginine (100 mg kg-1 I.V. bolus, 10 mg kg-1 h-1, 2 h infusion) and the NO donor glyceryl trinitrate (GTN) were given at the same time (20, 40 and 80 microg kg-1 min-1, 15 min infusion) as perfusion with indomethacin was started. Epithelial permeability was quantified by measuring blood-to-lumen clearance of 51Cr-labelled EDTA. Indomethacin caused a 20-fold increase in 51Cr-EDTA leakage compared with that of the control group. Treatment with L-NAME or L-arginine did not affect the indomethacin-induced alterations in mucosal permeability. Administration of GTN (20 microg kg-1 min-1) significantly reduced the indomethacin-induced mucosal dysfunction. By contrast, higher doses of GTN (80 microg kg-1 min-1) exacerbated epithelial dysfunction induced by indomethacin. Elevated levels of carbonyls and myeloperoxidase (MPO) observed after indomethacin administration were significantly reduced, to the control values, when GTN (20 microg kg-1 min-1) was administered along with indomethacin. These data suggest that NO from exogenous sources can exert a dual action on the integrity of the gastric mucosa challenged by indomethacin. Low doses of GTN can prevent mucosal dysfunction induced by indomethacin, while higher doses of GTN may exacerbate the increases in epithelial permeability.
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PMID:Role of nitric oxide in indomethacin-induced gastric mucosal dysfunction in the rat. 1022 73

A chemiluminescence (CL) assay has been used to measure the reactive oxygen species (ROS)-generating capacity of phagocytes. Primed neutrophils produce ROS and nitric oxide (NO) upon induction of nitric oxide synthase (NOS) activity. NO and superoxide (O(2)(-)) form peroxynitrite (ONOO(-)), and emit CL. We examined the involvement of NOS in the CL response of neutrophils using a method based on the modulation of enzyme activity of NOS by the substrate L-arginine and an inhibitor; L-NAME. We used lipopolysaccharide (LPS) as the neutrophil-priming agent. Addition of sodium azide (NaN(3)) with horseradish peroxidase (HRP) to luminol-dependent CL, gave a CL response that was significantly enhanced when 10 mmol/L L-arginine was present (p <0.05), suggesting that NOS activity contributed to the CL response of human neutrophils. LPS-primed luminol-dependent CL was significantly inhibited by L-NAME compared with D-NAME. The proportion of the difference between the two inhibitors in luminol-dependent CL was 12.3 +/- 15.0%. Therefore, approximately 12% of the LPS-primed luminol-dependent CL decrease induced by L-NAME indicated the contribution of NOS activity to the CL response.
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PMID:Contribution of nitric oxide synthase to human neutrophil chemiluminescence. 1060 4

BACKGROUND: This study was designed to examine the role of P-selectin expression in leukocyte adhesion to endothelium caused by inhibition of nitric oxide synthesis. METHODS AND RESULTS: Rat aortic rings were treated with the nitric oxide synthesis inhibitor N(omicron)-nitro-l-arginine methyl ester (l-NAME) for 2 hours. Parallel sets of aortic rings were pretreated with the nitric oxide precursor l-arginine or posttreated with a specific monoclonal antibody against P-selectin. Some rings were used for determination of vasoreactivity in response to norepinephrine and acetylcholine, while other rings were incubated with autologous unlabeled leukocytes or Biotin-FITC labeled leukocytes for 30 minutes. Leukocyte adhesion to vascular endothelium was determined by scanning electron microscopy. l-NAME enhanced the contractile response in response to norepinephrine, suppressed the relaxant response to acetyleholine, promoted leukocyte adherence to the endothelium and resulted in P-selectin expression on the aortic endothelium. Pretreatment of aortic rings with l-arginine reversed the l-NAME-mediated changes in vasoreactivity in response to norepinephrine and acetyleholine and attenuated the l-NAME-enhanced leukocyte adhesion to endothelial intima. P-selectin treatment, on the other hand, had no effect on l-NAME-mediated changes. Intraperitoneal administration of l-NAME resulted in a significant decrease in plasma nitrite level, a small, but significant, increase in lung and spleen myeloperoxidase activity, and a significant increase in leukocyte deposition in lung and spleen. The l-NAME-mediated increase in myeloperoxidase activity and leukocyte deposition in the spleen, but not in the lungs, was abolished by treatment of rats with the P-selectin antagonist CY1503 administered 30 minutes prior to l-NAME. CONCLUSIONS: These observations indicate that a reduction in nitric oxide synthesis enhances leukocyte adhesion to aortic endothelium and in visceral tissues. While P-selectin expression is evident in some of the experimental models of leukocyte adhesion to endothelium under conditions of nitric oxide inhibition, the role of P-selectin expression remains unclear.
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PMID:Nitric Oxide Synthesis Inhibition and Role of P-selectin in Leukocyte Adhesion to Vascular Tissues. 1068 48

A beneficial role of nitric oxide (NO) after cerebral ischemia has been previously attributed to its vascular effects. Recent data indicate a regulatory role for NO in initial leukocyte-endothelial interactions in the cerebral microcirculation under basal and ischemic conditions. In this study, the authors tested the hypothesis that endogenous NO production during and/or after transient focal cerebral ischemia can also be neuroprotective by limiting the process of neutrophil infiltration and its deleterious consequences. Male Sprague-Dawley rats were subjected to 2 hours occlusion of the left middle cerebral artery and the left common carotid artery. The effect of NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg, intraperitoneally), an NO synthase inhibitor, was examined at 48 hours after ischemia on both infarct size and myeloperoxidase activity, an index of neutrophil infiltration. L-NAME given 5 minutes after the onset of ischemia increased the cortical infarct volume by 34% and increased cortical myeloperoxidase activity by 60%, whereas administration of L-NAME at 1, 7, and 22 hours of reperfusion had no effect. Such exacerbations of infarction and myeloperoxidase activity produced when L-NAME was given 5 minutes after the onset of ischemia were not observed in rats rendered neutropenic by vinblastine. These results suggest that after transient focal ischemia, early NO production exerts a neuroprotective effect by modulating neutrophil infiltration.
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PMID:Modulation by nitric oxide of cerebral neutrophil accumulation after transient focal ischemia in rats. 1082 31

Effect of low-level exposure of quinalphos (QP) and cypermethrin (CP) on the blood-brain barrier (BBB) permeability to macromolecular tracers, Evans blue (EB) and horseradish peroxidase (HRP) was studied in developing rat pups. Ten-day-old rat pups were daily exposed to QP and CP at a dose of approximately 1/50th of adult LD50 through oral intubation, upto postnatal day 17 (PND). Functional integrity of the BBB was assessed by measuring the brain uptake index (BUI) of HRP and by visually grading the brains of control and treated rat pups for the staining of EB. Our results have demonstrated a significant increase in the BUI for HRP (204 and 254%) and have also shown a significant amount of EB staining in QP and CP exposed brains, respectively, as compared to the age-matched controls. Studies carried out with the nitric oxide synthase (NOS) inhibitor L-NAME (30 mg/kg, i.p., on alternate days from PND 10-17) have provided significant protection against the QP-induced increase in the BBB permeability, suggesting the possible involvement of NO in the barrier disruption. Microvessel acetylcholinesterase activity was also inhibited (53%, P<0.001) in QP-exposed rat pups only, with no change observed in CP-exposed microvessels. However, membrane fluidity was found to be decreased in both QP (18%, P<0.05) and CP (15%, P<0.05) exposed microvessels compared to controls. It is evident from the study that QP and CP exposure during early postnatal period causes significant impairment in the development and maturation of the BBB that may have adverse consequences on the normal brain functioning with long-term neurotoxic effects.
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PMID:Effect of quinalphos and cypermethrin exposure on developing blood-brain barrier: role of nitric oxide. 1086 65

The aim of this study was to investigate the effect of nitric oxide (NO) on the gastric injury induced by hemorrhagic shock. Hemorrhagic shock was created by withdrawing 3 ml blood/200 g body weight of the rats. Before the hemorrhage, N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v. bolus), D-NAME (10 mg/kg i.v. bolus), or L-arginine (100 mg/kg i.v. bolus and 10 mg/kg/min infusion) + L-NAME were administered. At the end of the 1-hour hypovolemic shock period, histological analysis, gastric ulcer index, gastric myeloperoxidase (MPO) activity, and gastric protein oxidation (PO) levels were determined. In histological analysis a destructive effect of L-NAME (NO synthase inhibitor) was demonstrated. L-NAME treatment increased gastric MPO activity, L-arginine reversed this effect and D-NAME had no effect. Tissue PO activity was found to be increased in L-NAME-treated rats; L-arginine treatment reversed this activity. It is concluded that gastric barrier function is altered after hemorrhagic shock, and L-arginine (NO precursor) can prevent mucosal injury in the stomach. This effect of NO may be on gastric blood flow and can be mediated by tissue neutrophils.
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PMID:Role of nitric oxide in gastric injury induced by hemorrhagic shock in rats. 1094 Jul 85

Chronic ingestion of xenobiotics could be pathogenic in the gastrointestinal tract. Recently, we showed that acute low administration of a food contaminant (diquat) induced intestinal secretion involving mast cells and nitric oxide. This work aimed to determine in rats: (1) the influence of a low level (0.1 mg/kg/day per os) chronic ingestion of diquat on gastrointestinal immune cells, and (2) the participation of nitric oxide synthases (NOS) in these effects. Diquat increased both gastric and jejunal myeloperoxidase activities, tissue histamine in vitro release after stimulation by 48/80, and mast cell numbers. Diquat did not alter gastric NOS but increased intestinal inducible NOS (iNOS) activity. L-NAME prevented diquat-induced gastric and intestinal mastocytosis and gastric but not intestinal inflammation. L-NAME reduced gastric constitutive NOS (cNOS) activity and reestablished control iNOS activity. Chronic low level ingestion of diquat induces a low-grade gastric and intestinal inflammation with mastocytosis and enhancement of intestinal iNOS activity.
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PMID:Chronic ingestion of a potential food contaminant induces gastrointestinal inflammation in rats: role of nitric oxide and mast cells. 1105 29

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