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)

Pulmonary granulomatous inflammation modulated by IFN-gamma and IL-12 is also associated with augmented inducible nitric oxide synthase (NOS II). To address the role of increased nitric oxide synthesis in this model, mice received daily i.p. injections of NG-nitro-L-arginine-methyl ester (L-NAME; 8 mg/kg) during both the 2-wk immunization period with purified protein-derivative (PPD) and the subsequent lung challenge with PPD-coated Sepharose beads. Other groups of animals received saline, L-NAME or NG-nitro-D-arginine-methyl ester (D-NAME; 8 mg/kg) during the pulmonary embolization period and not the PPD sensitization period. On day 4 post-PPD bead challenge, PCR analysis of the whole lung revealed that NOS II expression appeared to be similar in both of the L-NAME treatment protocols. L-NAME-treated mice in both dosing protocols had lung lesions that were significantly larger than granuloma lesions measured in mice that received saline or D-NAME. The enlarged lesions from L-NAME-treated mice contained markedly greater numbers of neutrophils and eosinophils. Equivalent numbers of PPD-activated dispersed cells from whole lungs of L-NAME-treated mice produced significantly higher levels of IL-4 and IL-10 and smaller amounts of IL-12 and IFN-gamma compared with similar lung cultures derived from control or D-NAME-treated mice. Levels of C-C chemokines such as monocyte chemoattractant protein-1 (MCP-1), C10, and macrophage inflammatory protein-1alpha (MIP-1alpha) were also significantly elevated in lung cultures from L-NAME-treated mice compared with controls. Thus, nitric oxide regulates the size and cellular composition of the Th1-type lung granuloma, possibly through its effects on the cytokine and chemokine profile associated with this lesion.
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PMID:Alteration of the cytokine phenotype in an experimental lung granuloma model by inhibiting nitric oxide. 954

In vivo injection of the edible frog Rana esculenta with NOS inhibitor, L-NMMA caused prolongation of skin allograft and xenograft viability, statistically significant only in the latter case. In the present studies skin allo- and xenografts at the latent or rejection phase were excised from the hosts (Bufo bufo, R. temporaria, and R. esculenta) and incubated in vitro for 24 hrs in a medium only or in the presence of competitive (L-NMMA, L-NAME, L-aminoguanidyne) and noncompetitive (dexamethasone and cycloheximide) inhibitors of NO synthesis. In some experiments graft infiltrating cells were washed out and cultured separately from the respective skin fragments. The nitrite level was measured in the culture supernatant using Griess reagent. The nitrite level was negligible in the control skins, autografts, and xenografts depleted of graft infiltrating cells, as well as in allo- and xenografts excised at the rejection phase. In the case of grafts excised at the latent phase, the nitrite amount was substantial in supernatant from allografts and significantly higher in xenografts. A high level of nitrite was also present in supernatants from graft infiltrating cells. It is concluded that the NO contributes to some stages of the rejection process of the anuran skin grafts, this contribution being especially significant in the case of xenografts. The main source of this agent are graft infiltrating phagocytic cells.
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PMID:Nitric oxide production by cells infiltrating amphibian skin grafts. 955 39

1. Intraplantar injection of carrageenan (150 microl, 1-3% w/v) in the rat resulted in a dose-related increase in hindpaw weight (oedema) characterized by a rapid 'early' phase (up to 2.5 h) response followed by a more sustained 'late' phase (2-6 h) response. No change in weight of either the contralateral (i.e. noninjected) hindpaw or hindpaws injected with saline was observed. 2. Six hours after intraplantar injection of carrageenan (1-3% w/v) hindpaw constitutive (i.e. calcium-dependent) nitric oxide synthase (cNOS) activity (determined ex vivo as the conversion of radiolabelled L-arginine to radiolabelled citrulline) was increased (e.g. 2% w/v; 0.64+/-0.08 pmol citrulline mg(-1) protein 15 min(-1) c.f. 0.08+/-0.04 pmol citrulline mg(-1) protein 15 min(-1) in saline-injected, control animals, n=4, P<0.05). Carrageenan injection also resulted in the appearance in hindpaw homogenates of inducible (i.e. calcium-independent) nitric oxide synthase (iNOS, e.g. 2% w/v; 0.67+/-0.14 pmol citrulline mg(-1) protein 15 min(-1), n=4). Hindpaw cyclic GMP concentration was also significantly increased 6 h after intraplantar injection of carrageenan (e.g. 2% w/v; 379.6+/-26.8 fmol mg(-1) protein c.f. 261.8+/-42.2 fmol mg(-1) protein, in saline-injected, control animals, n=4, P<0.05). 3. Pretreatment (5-25 mg kg(-1), i.p., 30 min before carrageenan, 2% w/v) of animals with L-N(G) nitro arginine methyl ester (L-NAME; isoform nonselective inhibitor of NOS) or 7-nitro indazole (7-NI; inhibitor of neuronal NOS, nNOS) caused dose-related inhibition of both the early (2 h) and late (6 h) phase hindpaw oedema, associated with reduced hindpaw iNOS and cNOS activity and cyclic GMP concentration in animals killed at 6 h. Administration of 7-NI (5-25 mg kg(-1), i.p.) to animals 2.5 h after intraplantar carrageenan (2% w/v) injection (i.e. at the end of the early phase oedema response) produced dose-related inhibition of the late phase response. 4. Pretreatment (5-25 mg kg(-1), i.p., 30 min before carrageenan, 2% w/v) of animals with L-N6-iminoethyllysine (L-NIL, selective inhibitor of iNOS) (5-25 mg kg(-1)) failed to affect the early phase hindpaw oedema response but did produce a dose-related inhibition of the late phase oedema. L-NIL pretreatment also inhibited the carrageenan-induced increase in both hindpaw iNOS and cNOS activity as well as the rise in hindpaw cyclic GMP concentration. 5. The present experiments demonstrate an anti-inflammatory effect of 7-NI as evidenced by inhibition of carrageenan-induced hindpaw oedema in the rat. Inhibition of nNOS (early phase) and iNOS (late phase) at the site of inflammation most probably accounts for the anti-inflammatory activity observed. These data suggest a role for nitric oxide synthesized by the nNOS isoform (most probably within sensory nerves) in this model of inflammation.
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PMID:A comparison of the effects of L-NAME, 7-NI and L-NIL on carrageenan-induced hindpaw oedema and NOS activity. 955 95

1. Rats challenged with lipopolysaccharide (LPS) produce large amounts of nitric oxide (NO) following the induction of the inducible NO-synthase (iNOS) in several tissues and organs. Recent studies have shown that the expression of iNOS is regulated at the transcriptional level by a transcription nuclear factor-kappaB (NF-kappaB). In this study we investigated the role of NO in a model of LPS-induced plasma-leakage in rat skin and the involvement of NF-kappaB. 2. Plasma leakage in the rat skin was measured over a period of 30 min to 2 h as the local accumulation of intravenous (i.v.) injection of [125I]-human serum albumin ([125I]-HSA) in response to intradermal (i.d.) injection of LPS. LPS (1, 10, 100 microg/site) produced a dose-related increase in plasma extravasation (18.2+/-3.2, 27.2+/-2.9, 40.4+/-9.6 microl/site) as compared to saline control (11.4+/-2.2 microl/site). This increase was maximal after 2 h; therefore this time point and the dose of LPS 10 microg/site was used in all the successive experiments. 3. To investigate the role of NO in LPS-induced plasma leakage in rat skin, the non-selective NOS inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the more selective iNOS inhibitor S-methyl-isothiourea (SMT) was injected i.d. with LPS. L-NAME and SMT (0.01, 0.1 and 1 micromol/site) inhibited LPS-induced plasma leakage in a dose-related fashion (L-NAME: 26.0+/-5.5, 20.2+/-1.6, 18.0+/-2.0 microl/site; SMT: 19.5+/-1.5, 17.0+/-1.6, 15.0+/-2.6 microl/site) as compared to LPS alone (27.2+/-2.9 microl/site). At the lowest concentration used (0.01 micromol/site), SMT significantly reduced plasma leakage by 30%+/-0.7 while L-NAME (0.01 micromol/site) was not effective. 4. Treatment with increasing concentrations of pyrrolidinedithyocarbamate (PDTC) (0.01, 0.1, 1 micromol/site), an inhibitor of NF-kappaB activation, injected i.d. 30 min before LPS challenge, inhibited in a concentration-dependent fashion LPS-induced plasma leakage by 9.0+/-0.6, 33+/-4.0, 51+/-2.0% respectively. Moreover, PDTC (0.1, 1 micromol/site) suppressed LPS-induced NF-kappaB DNA-binding. 5. Western blot analysis showed significant levels of iNOS proteins in the skin samples of LPS-treated rats, as compared to basal levels present in saline-injected rat skin. PDTC (0.1, 1.0 micromol/site) dose-dependently decreased the amount of iNOS protein expression induced by LPS. 6. Our results indicate that LPS-induced plasma leakage in rat skin is modulated by NO mainly produced by the inducible isoform of NOS. Furthermore, the suppression of plasma leakage by PDTC, an inhibitor of NF-kappaB activation, is correlated to the inhibition of iNOS protein expression.
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PMID:Evidence that inducible nitric oxide synthase is involved in LPS-induced plasma leakage in rat skin through the activation of nuclear factor-kappaB. 957 26

1. Previous study showed that N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric bxide synthase, induces catalepsy in a dose-dependent manner in male albino-Swiss mice. 2. The objective of the present work was to further investigate this effect, extending it to other NOS inhibitors. 3. Results showed that L-NOARG (40-80 mg/kg i.p.), N(G)-nitro-L-arginine methylester (L-NAME, 40-160 mg/kg i.p.) or N(G)-monomethyl-L-arginine (L-NMMA, 80 mg/kg i.p.) were able to induce catalepsy in mice. The effect of L-NOARG (40 mg/kg) was antagonized by pretreatment with L-arginine (300 mg/kg), but not by D-arginine (300 mg/kg). The catalepsy-inducing effect of L-NOARG suffered rapid tolerance, showing a significant decrease after two days of chronic treatment (40 mg/kg i.p., twice a day). 4. The results suggest that interference with the formation of nitric oxide induces significant motor effects in mice.
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PMID:Catalepsy induced by nitric oxide synthase inhibitors. 958 Jan 28

In this study we tested the hypothesis that nitric oxide (NO), which function as a novel type of inter-cellular messenger in the central nervous system (CNS) participated in the facilitator effect of arginine vasopressin (AVP) on learning and memory. Recent investigations have provided evidences that inhibition of NO synthesis attenuated the vasodilatation caused by AVP, and inhibited the improvement of learning and memory evoked by angiotensin II. AVP as well as pharmacologically produced increase in endogenous NO facilitates the consolidation of shock avoidance learning. We evaluated the behavioural effects of AVP at dose 1 microgram after the inhibition of NOS by NG-nitro-L-arginine methyl ester (L-NAME) at dose 10 micrograms, and after the injection of endogenous donor of NO -L-arginine- 10 micrograms in the retrieval of passive avoidance situation, and in consolidation of active avoidance responses. The locomotor activity of all investigated drugs was tested in the open field test. AVP facilitated the recall of passive avoidance responses and consolidation of active avoidance responses. Neither the increase of NO concentration after the injection of L-arginine nor the decrease of NO after the inhibition of NOS by L-NAME changed the behavioural effects of AVP. L-arginine increased the psychomotor behaviour and L-NAME decreased the activity of animals in the "open field" test. L-arginine itself improved the consolidation of active avoidance responses. Our results indicate that central action of AVP is probably independent of NO concentration in the brain.
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PMID:The participation of nitric oxide in the facilitator effect of arginine vasopressin on memory. 958 86

The role of mitochondrial energy metabolism in glutamate mediated neurotoxicity was studied in rat neurones in primary culture. A brief (15 min) exposure of the neurones to glutamate caused a dose-dependent (0.01-1 mM) increase in cyclic GMP levels together with delayed (24 h) neurotoxicity and ATP depletion. These effects were prevented by either the nitric oxide (.NO) synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (NAME; 1 mM) or by the N-methyl-D-aspartate (NMDA) glutamate-subtype receptor antagonist D-(-)-2-amino-5-phosphonopentanoate (APV; 0.1 mM). Glutamate exposure (0.1 mM and 1 mM) followed by 24 h of incubation caused the inhibition of succinate-cytochrome c reductase (20-25%) and cytochrome c oxidase (31%) activities in the surviving neurones, without affecting NADH-coenzyme-Q1 reductase activity. The rate of oxygen consumption was impaired in neurones exposed to 1 mM glutamate, either with glucose (by 26%) or succinate (by 39%) as substrates. These effects on the mitochondrial respiratory chain and neuronal respiration, together with the observed glutathione depletion (20%) by glutamate exposure were completely prevented by NAME or APV. Our results suggest that mitochondrial dysfunction and impairment of antioxidant status may account for glutamate-mediated neurotoxicity via a mechanism involving .NO biosynthesis.
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PMID:Glutamate neurotoxicity is associated with nitric oxide-mediated mitochondrial dysfunction and glutathione depletion. 959 99

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 vasodilator nitric oxide (NO) is involved in the regulation of systemic blood pressure and local organ blood flow. Inhibitors of the constitutively expressed nitric oxide synthase in endothelial cells (eNOS), e.g., Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME), aggravated liver injury in a variety of models. On the other hand, inhibitors of the inducible NOS (iNOS), e.g., 2-aminoethyl-isothiourea (AET), were found to be beneficial during endotoxemia. The aim of this investigation was to study the effect of AET compared with L-NAME on liver microvascular blood flow and injury in more complex models with multiple insults, i.e., ischemia (20 min)-reperfusion (8 h) in combination with .5 mg/kg endotoxin (IRE). Male Fisher rats were treated with 10 mg/kg AET or L-NAME and subjected to IRE. At 8 h, liver injury (plasma ALT: 1320+/-164 U/L) was significantly increased in AET-treated (5,018+/-1,379 U/L) and L-NAME-treated groups (2,429+/-228 U/L). Each inhibitor attenuated microvascular blood flow (assessed by laser Doppler flowmetry) to a similar degree. In striking contrast, AET completely reversed the endotoxin-induced impairment of the microvascular blood flow and significantly protected against an endotoxin-induced liver injury (plasma ALT: 3,007+/-268 U/L (ET); 460+/-39 U/L (ET+AET)). Infusion of endothelin-1 reduced microvascular blood flow by 50-60% and caused liver injury. Our data demonstrated that an inhibitor of eNOS (L-NAME) has a consistent detrimental effect on liver injury during ischemia-reperfusion and endotoxemia mainly because it can cause additional ischemia by reducing the microvascular blood flow. However, selective inhibitors of iNOS (AET) can impair hepatic blood flow and aggravate the injury or improve blood flow and attenuate organ injury depending on the experimental model. These results suggest that iNOS inhibitors may not be universally beneficial and should be tested in a variety of experimental models of sepsis/endotoxemia before used in clinical settings.
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PMID:Differential effect of 2-aminoethyl-isothiourea, an inhibitor of the inducible nitric oxide synthase, on microvascular blood flow and organ injury in models of hepatic ischemia-reperfusion and endotoxemia. 968 86


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