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)

This study provides direct evidence from measurements of its metabolites, NO2- and NO3-, that NO is released in the spinal cord during central sensitization. A microdialysis fiber was implanted in the dorsal horn at L5 for collecting dialysate and administering drugs. Dialysate was pumped through a cadminum reducing column, a post-column derivatizing unit, and then a u.v. detector. After injection of capsaicin into one hind foot, NO2-increased in the dialysate. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) significantly reduced NO release induced by a second injection of capsaicin into the opposite foot. This supports the ideas that NO is involved in central sensitization in the spinal cord and contributes to hyperalgesia and allodynia following capsaicin injection.
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PMID:Nitric oxide contributes to central sensitization following intradermal injection of capsaicin. 955 21

The correlation between endogenous nitric oxide (NO) generation and prostaglandin biosynthesis was studied in rat carrageenin pleurisy induced by the injection of 0.2 mL of 1% lambda-carrageenin into the pleural cavity. The pleural exudate was collected at 4 hr and the amounts of NO2- + NO3- (NOx) and prostaglandin E2 (PGE2) measured. The NOx present in the inflammatory exudate was determined by measuring the NO2- with the Griess reaction, after the reduction of NO3- to NO2- using acid-washed cadmium powder. PGE2 was measured by radioimmunoassay. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 1-3-10 mg/kg subcutaneously) reduced NOx by 20 +/- 7%, 41 +/- 6% and 55 +/- 9% (P < 0.01) and PGE2 by 9 +/- 6%, 41 +/- 11% and 74 +/- 9% (P < 0.001). Conversely, L-arginine (300 mg/kg SC) increasedNOx by 39 +/- 7% (P < 0.01) and PGE2 by 78 +/- 6% (P < 0.001). The NO scavenger haemoglobin (Hb), coinjected into the pleural cavity (3 mg/site) with carrageenin, produced a parallel inhibition of NOx (65 +/- 16%, P < 0.001) and PGE2 (71 +/- 18%, P < 0.001). The soluble guanylate cyclase inhibitor methylene blue (Mb; 2 mg/site) had no effect. Moreover haemoglobin, but not methylene blue, was able to significantly suppress the L-arginine-induced increase of both NOx and PGE2. In each pleural exudate, independently from the animal treatment, the amount of NOx was highly correlated to the amount of PGE2 (r = 0.93, P < 0.001). These results suggest that in rat carrageenin pleurisy the modulation of the L-arginine:NO pathway results in a parallel modulation of prostaglandin biosynthesis. The interaction between cyclooxygenase and the NO pathway may represent an important mechanism for the modulation of the inflammatory response.
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PMID:Relationship between nitric oxide and prostaglandins in carrageenin pleurisy. 960 35

Micropuncture studies of single nephrons have shown that macula densa solute reabsorption via a furosemide-sensitive pathway activates nitric oxide (NO) generation via neuronal NO synthase (nNOS). This pathway is enhanced during salt loading. We investigated the hypothesis that changes in NO generation via nNOS in the macula densa contribute to changes in whole kidney NO generation and action during alterations in salt intake. Groups of rats (n = 6-10) were equilibrated to high-salt (HS) or low-salt (LS) diets and were administered a vehicle (Veh), 7-nitroindazole (7-NI; a relatively selective inhibitor of nNOS), or furosemide (F; an inhibitor of macula densa solute reabsorption) with volume replacement. Compared with LS, excretion of the NO metabolites, NO2 plus NO3 (NOX) was increased during HS (LS: 9.0 +/- 0.5 vs. HS: 15.7 +/- 0.8 micromol/24 h; P < 0.001), but this difference was prevented by 7-NI (LS: 7.4 +/- 1.3 vs. HS: 9.4 +/- 1.6 micromol/24 h; NS). During nonselective blockade of NOS with NG-nitro-L-arginine methyl ester (L-NAME), renal vascular resistance (RVR) increased more in HS than LS (HS: +160 +/- 17 vs. LS: +83 +/- 10%; P < 0.001). This difference in response to nonselective NOS inhibition was prevented by pretreatment with 7-NI (HS: +28 +/- 6 vs. LS: +34 +/- 8%; NS) or F with volume replacement (HS: +79 +/- 11 vs. LS: +62 +/- 4%; NS). In conclusion, compared with salt restriction, HS intake increases NO generation and renal action that depend on nNOS and macula densa solute reabsorption.
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PMID:NO generation and action during changes in salt intake: roles of nNOS and macula densa. 960 12

This study was designed to test the hypothesis that nitric oxide (NO) mediates the blunted splenic sympathetic response to lipopolysaccharide (endotoxin) that occurs in young rats exposed to alcohol in utero (FAE). The subjects, 26-29-day-old rats, were progeny of pregnant dams fed an alcohol diet (35% of the calories were derived from ethanol) or their control and pair-fed (PFC) cohorts. We examined the effects of lipopolysaccharide (LPS) (0.5 mg/kg, i.p.) on splenic norepinephrine (NE) turnover, an index of sympathetic neural activity, splenic inducible NO synthase (iNOS) protein immunoreactivity, and NO metabolites nitrite/nitrate concentrations in plasma. In response to LPS, splenic NE turnover was increased by more than twofold in the PFC groups, but the increase did not occur in their FAE cohorts. The blockade of NOS with L-NAME (30 mg/kg, i.p.) reversed this difference. In both the PFC and FAE rats, basal levels of splenic iNOS protein immunoreactivity were equally barely detected and plasma NO metabolite levels were relatively low (25 microM in both groups). In response to LPS, however, iNOS protein displayed a marked increase in the PFC group and an even greater increase (by close to threefold) in the FAE rats. LPS also substantially increased plasma NO metabolite levels by close to eightfold in the control groups, but by 15-fold in their FAE cohorts compared to the basal levels. These findings support the hypothesis that in the FAE rat, an augmented NO formation accounts for the blunted sympathetic response to endotoxin.
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PMID:Splenic sympathetic response to endotoxin is blunted in the fetal alcohol-exposed rat: role of nitric oxide. 965 Jun 32

The role of the cholinergic and peptidergic pathways in the impairment of gastric motility associated with diabetic gastroparesis was assessed at the postsynaptic level using isolated fundus smooth muscle strips. Maximal contractile responses to carbachol and galanin were significantly decreased in fundus strips isolated from rats rendered diabetic by a single intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) 1, 4 and 8 weeks before experiments. We also observed notable decrements in the slopes and Hill's coefficients without conspicuous changes in the EC50 of the respective galanin concentration-response curves measured in strips obtained from STZ animals after 4 and 8 weeks. L-NAME reversed the above-mentioned alterations in an L-arginine-sensitive manner in STZ rats after 4 weeks but not in STZ rats after 8 weeks. The blood plasma nitrite/nitrate levels in STZ animals after 4 and 8 weeks were increased by 44.6 and 61.9%, respectively. Ca2+-independent nitric oxide synthase activity in gastric fundus strips and stomach corpus mucosa from STZ rats after 4 weeks was markedly enhanced by 37.4 and 31.9%, respectively, suggesting an enhanced nitric oxide production. In vivo insulin treatment prevented diabetes-induced alterations in smooth muscle contractility. We conclude that the smooth muscle dysfunction evoked by experimental diabetes causing diminished contractions of fundus strips to carbachol and galanin is at least partly due to the increased nitric oxide synthesis.
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PMID:Effects of diabetes mellitus on the contractile activity of carbachol and galanin in isolated gastric fundus strips of rats. 969 Dec 26

We investigated whether a complete inhibition of nitric oxide (NO) formation caused by bacterial endotoxin (lipopolysaccharide, LPS) in vivo prevents the hypotension and restores the vascular hyporeactivity to normal in vivo and ex vivo. The combination of dexamethasone (Dex; 3 mg/kg at 30 min before LPS) plus aminoguanidine (AG; 15 mg/kg at 2 h after LPS) inhibited the overproduction of nitrate (an indicator of NO) in the plasma and aortic smooth muscle and also prevented the development of the delayed hypotension in rats treated with LPS for 6 h. However, the vascular hyporeactivity to norepinephrine (NE) was only partially improved either in vivo or ex vivo in endotoxemic rats treated with Dex plus AG. Pretreatment of aortic rings with Nomega-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2, 4]oxidazolo[4,3-a]quinoxalin-1-one (ODQ) enhanced the contraction to NE in rings obtained from LPS-treated rats, but not in those from Dex plus AG-treated endotoxemic rats. Methylene blue, an inhibitor of soluble guanylyl cyclase (GC), completely restored contractions to NE and aortic cGMP levels to normal either in LPS-treated rats or in Dex plus AG-treated endotoxemic rats, whereas the cGMP level was partially inhibited by ODQ in LPS-treated rats only. These results suggest that non-NO mediator(s) also activates soluble GC during endotoxemia. Interestingly, we found that in the presence of tetraethylammonium (an inhibitor of K+ channels) plus L-NAME or charybdotoxin [a specific inhibitor of large-conductance Ca2+-activated K+ (KCa) channels] plus ODQ, the vascular hyporeactivity to NE in the LPS-treated group was also completely restored to normal. In addition, in the presence of L-NAME or ODQ, the vascular hyporeactivity to high K+ was abolished in rings from the LPS-treated group. These results suggest that LPS causes the production of other mediator(s), in addition to NO, which also stimulates soluble GC (i.e., increases the formation of cGMP) and then activates the large-conductance KCa channels in the vascular smooth muscle causing vascular hyporeactivity.
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PMID:Nitric oxide-independent activation of soluble guanylyl cyclase contributes to endotoxin shock in rats. 974 61

The aim of this work was to determine if the inhibition or stimulation of NO synthesis modulates liver damage induced by the chronic administration of CCl4. CCl4 was administered three times a week for 8 weeks to male Wistar rats treated simultaneously with N omega-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg, p.o., twice a day), aminoguanidine (AG, 4 g/L in the drinking water), or L-arginine (500 mg/kg, p.o., twice a day); appropriate controls were performed. Serum NO2- + NO3- increased in the groups treated with CCl4 and/or L-arginine, but the effect was prevented by either L-NAME or AG. In the liver, lipid peroxidation and collagen content increased, while glycogen content decreased in the CCl4-treated group (P < 0.05); L-NAME and AG accentuated these effects. Serum enzyme activities of alanine aminotransferase (ALT), alkaline phosphatase, and gamma-glutamyl transpeptidase (gamma-GTP) and bilirubin content increased about 2-, 3-, 2-, and 6-fold, respectively, after CCl4 intoxication (P < 0.05); L-NAME or AG cotreatment further increased the enzyme activities (P < 0.05). L-Arginine treatment protected the liver partially from the elevation of collagen, bilirubins, and alkaline phosphatase and from glycogen depletion induced by CCl4 intoxication (P < 0.05), but showed no significant effect on ALT, gamma-GTP, or lipid peroxidation. These results suggest that NO protects the liver against oxidative injury, because NO inhibition by L-NAME or AG increased lipid peroxidation and the other markers of liver injury studied herein.
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PMID:Nitric oxide protection of rat liver from lipid peroxidation, collagen accumulation, and liver damage induced by carbon tetrachloride. 975 Oct 83

After removing nonspecific immunoreactivities from crude extract by immunoaffinity chromatography, an immunoreactive-band at 60 kDa of constitutive nitric oxide synthase (cNOS) from Saccharomyces cerevisiae was detected by Western blot using mouse monoclonal anti-neuronal NOS (cNOS). The activity of yeast cNOS, which was prepared by either histone-agarose chromatography or anti-neuronal NOS immunoprecipitation, was monitored by the formation of citrulline. Yeast cNOS was activated in the presence of calmodulin and arginine, whereas it was inhibited by L-NAME, a mammalian NOS inhibitor. Moreover, actinomycin-D decreased the extracellular and the intracellular levels of nitrate and nitrite which had been converted from NO. The results suggest that cNOS occurs in unicellular eukaryotes and the enzyme activity can be regulated.
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PMID:Constitutive nitric oxide synthase in Saccharomyces cerevisiae. 976 6

Experiments were conducted to determine whether Sprague-Dawley rats from different suppliers have the same hypertensive response to chronic inhibition of nitric oxide synthase. Rats (240-260 g) obtained from either Harlan or Charles River Laboratories were maintained in metabolic cages for baseline (week 0) measurements before receiving Nomega-nitro-L-arginine methyl ester (L-NAME) in the drinking water for 2 wk at 5 or 65 mg . kg-1 . day-1. Baseline values for tail cuff pressure (TCP) were significantly higher in Harlan rats (131 +/- 2 mmHg) compared with Charles River rats (108 +/- 3 mmHg, P < 0.001). At 65 mg . kg-1 . day-1, L-NAME produced a significantly larger increase in TCP in Harlan versus Charles River rats (41 +/- 4 vs. 29 +/- 4%, respectively, P < 0.01). Food and water intake and sodium and water excretion were not different between groups. Urinary excretion of nitrate and nitrite (UNOxV) was significantly reduced in all rats given L-NAME. UNOxV was decreased by 69 +/- 12 and 62 +/- 7% in Harlan and Charles River rats, respectively. The lower dose of L-NAME increased TCP and decreased UNOxV in both Harlan and Charles River rats; these effects were more pronounced in the Harlan rats. These results suggest that NO plays a more significant role in the maintenance of arterial pressure in Sprague-Dawley rats from Harlan compared with Charles River Laboratories. Such findings may also provide insight as to why some of the mechanisms associated with chronic L-NAME treatment are not consistent between laboratories.
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PMID:Hypertensive response to chronic NO synthase inhibition is different in Sprague-Dawley rats from two suppliers. 979 Oct 95

Excess production of nitric oxide contributes to the refractory hypotension associated with sepsis and is dependent upon precursor availability, L-arginine. Endothelial uptake of L-arginine by the y+ transporter can be inhibited by another cationic amino acid, L-lysine. This study was undertaken to determine the effects of L-lysine in an anaesthetized ovine model of endotoxaemia in which nitric oxide production is known to be limited by L-arginine availability. The haemodynamic effects of i.v. L-lysine (500 mg kg-1) were compared with those of a known inhibitor of nitric oxide synthase, NG-nitro-L-arginine-methyl ester, L-NAME (25 mg kg-1) and with control animals (n = 6 per group). Serum nitrates, the stable end metabolite of nitric oxide production, were also measured. L-NAME administration caused a significant increase in systemic and pulmonary vascular resistance (P < 0.0001), mean arterial pressure (P < 0.0001) and a reduction in serum nitrate concentrations (P < 0.0001). The administration of L-lysine had no effect on systemic or pulmonary vascular resistance, mean arterial pressure or serum nitrate concentrations. We conclude that the administration of L-lysine does not inhibit nitric oxide production in this model.
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PMID:Effect of L-lysine on nitric oxide production in ovine endotoxaemia. 981 21


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