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

The effects of trypsin and arginine analogues, alone or in combination, on half-maximal non-adrenergic, non-cholinergic (NANC) relaxation elicited by different pulse trains of electrical field stimulation were studied in the rat gastric fundus in order to investigate further the relative contribution of peptides and NO. Trypsin (1 microM) partially inhibited electrically-induced NANC relaxation especially when longer pulse trains were used. L-NOARG, L-NAME and L-NMMA, but not D-NOARG or D-NAME (3-300 microM) produced concentration-dependent inhibition of the electrically induced NANC relaxation. L-Arginine (L-Arg), but not D-Arginine (D-Arg) (3.8 microM-3.8 mM) produced a concentration-dependent reversal of the inhibitory effect of L-NOARG IC50 (38 microM). Neither L-NOARG (38 microM) nor L-Arg (380 microM) influence submaximal relaxation induced by VIP (3 nM), isopropylnoradrenaline (10 nM), ATP (10 microM) or sodium nitroprusside (300 nM). Moreover L-NOARG (100 microM) did not influence neurally-induced VIP release. L-NOARG inhibition of NANC relaxation was significant only when short pulse trains were used, while trypsin showed significant inhibition only of relaxation induced by longer pulse trains. These results suggest that the relaxation induced by the activation of the NANC inhibitory neurotransmission of the rat gastric fundus consists of at least two components, one trypsin-sensitive and the other trypsin-resistant, to which VIP and NO contribute, respectively.
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PMID:Evidence for dual components in the non-adrenergic non-cholinergic relaxation in the rat gastric fundus: role of endogenous nitric oxide and vasoactive intestinal polypeptide. 158 95

1. The aim of this investigation was to study the relationship between contractile responsiveness, activation of the L-arginine pathway and tissue levels of guanosine 3':5'cyclic monophosphate (cylic GMP) in aortic rings removed from rats 4 h after intraperitoneal administration of bacterial endotoxin (E. coli. lipopolysaccharide, LPS, 20 mg kg-1). 2. LPS-treatment resulted in a reduction of the sensitivity and maximal contractile response to noradrenaline (NA). 3. Depression of the maximal contractile response was restored to control by 6-anilo-5,8-quinolinedione (LY 83583, 10 microM), which prevents activation of soluble guanylate cyclase. 4. Cyclic GMP levels in tissue from LPS-treated rats were 2 fold greater than cyclic GMP levels detected in tissue from control (saline-treated) rats. The LPS-induced increase in cyclic GMP content was observed both in the presence and absence of functional endothelium. 5. Addition of L-arginine 1 mM) to maximally contracted aortic rings produced significantly relaxation of rings from LPS-treated rats but not rings from control animals. In the LPS-treated group, addition of L-arginine was also associated with a significant increase in cyclic GMP content. L-Arginine had no effect on the cyclic GMP content of control rings. D-Arginine (1 mM) was without effect. 6. In rings from LPS-treated rats, NG-nitro-L-arginine methyl ester (L-NAME, 300 microM), an inhibitor of nitric oxide (NO) production, increased the contractile response to NA and prevented the LPS-induced increase in cyclic GMP content. In control rings, L-NAME increased the NA sensitivity only when the endothelium remained intact and reduced the cyclic GMP content of these rings to that of control endothelium-denuded rings. 7. These results demonstrate that LPS-induced hyporeactivity to NA occurs secondarily to activation of the L-arginine pathway and subsequent activation of soluble guanylate cyclase in vascular tissue. In addition they suggest that LPS induces the production of an NO-like relaxing factor in non-endothelial cells.
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PMID:Evidence that an L-arginine/nitric oxide dependent elevation of tissue cyclic GMP content is involved in depression of vascular reactivity by endotoxin. 167 81

1. The effects of L-NG-nitro-arginine (L-NOARG) and some other arginine analogues on non-adrenergic, non-cholinergic (NANC) relaxations of the rat anococcygeus muscle were investigated. 2. L-NOARG (5-200 microM) produced concentration-related inhibition of the NANC response; 100 microM L-NOARG produced 90% inhibition. 3. L-Arginine (5-200 microM) produced a concentration-related reversal of the inhibitory effect of 20 microM L-NOARG; a five fold excess of L-arginine (100 microM) was required to obtain the maximum reversal of 90%. D-Arginine (100 microM) produced no such reversal, but significant reversal was produced by L-citrulline, L-arginine-L-aspartate, L-homoarginine and L-arginine-methyl-ester (all at 100 microM). 4. L-NG-nitro-arginine-methyl-ester (L-NAME; 5-200 microM) also reduced NANC relaxations, with a potency similar to that of L-NOARG; both L-NOARG and L-NAME were some ten times more potent than L-NG-monomethyl-arginine (L-NMMA). Like L-NOARG, the effects of L-NAME (20 microM) were reversed by 100 microM L- but not D-arginine. 5. Neither L-NOARG nor L-NAME (both 20 microM) affected submaximal relaxations induced by 10 microM sodium nitroprusside or 20 microM hydroxylamine. 6. D-NOARG, L-NG-tosyl-arginine and L-N alpha-(t-butyl-oxycarbonyl)-NG-nitro-arginine (all at 100 microM) had no effect on NANC relaxations. 7. Thus, in the rat anococcygeus, L-NOARG and L-NAME are more potent than L-NMMA as prejunctional inhibitors of NANC transmission. The reversibility of the effect of L-NOARG by arginine analogues suggests that the NANC system of the anococcygeus shows similarities to the endogenous nitrate system recently described in the brain.
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PMID:L-NG-nitro-arginine and its methyl ester are potent inhibitors of non-adrenergic, non-cholinergic transmission in the rat anococcygeus. 216 39

Kainic acid (KA)-sensitive receptors are located on primary afferent C-fibers. Behavioral sensitization to each of four repeated injections of KA appears to involve activation of primary afferent C-fibers based on its susceptibility to capsaicin pretreatment. Hyperalgesia, thought to involve transmission along C-fibers, is sensitive to pharmacologic manipulation of nitric oxide (NO). We tested the hypothesis that KA activates C-fibers, either directly or indirectly, by a mechanism that involves NO. Pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, inhibited KA sensitization whereas D-NAME, the inactive isomer, failed to mimic this action. D-Arginine also inhibited sensitization to KA, whereas L-arginine, a NO precursor, was inactive when administered alone but reversed the inhibitory effect of L-NAME. Methylene blue, which inhibits guanylyl cyclase and NO synthase, attenuated KA sensitization, suggesting that cyclic GMP synthesis may also be involved in this phenomenon. Reduced hemoglobin, which sequesters NO in the extracellular space, attenuated KA sensitization, indicating that the effect of NO is brought about in structures adjacent to cells in which it is synthesized. This convergence of data is consistent with the mediation of behavioral sensitization to KA by NO. KA sensitization has been shown to involve an action of the NH2 terminus of substance P (SP) and NO may thus mobilize SP. Consistent with this, in the presence of SP(1-7), methylene blue was no longer able to inhibit sensitization to KA, suggesting that NO evokes, rather than results from, mobilization of SP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sensitization to the behavioral effect of kainic acid in the mouse is mediated by nitric oxide. 747 37

Human monocytes (M phi) require stimulation with substances such as bacterial endotoxin [LPS (lipopolysaccharide)] to produce angiogenic activity. In this study, we report that stimulation of M phi with LPS (5 micrograms/ml) in the absence of L-arginine greatly reduced their production of angiogenic activity, as assessed in vivo in rat corneas and in vitro by chemotaxis of human umbilical vein endothelial cells (HU-VECs). D-Arginine did not substitute for L-arginine in the production of angiogenic activity. The nitric oxide synthase (NO synthase, EC 1.14-13.39) inhibitors NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME) both inhibited the production of angiogenic activity by LPS-stimulated M phi in the presence of L-arginine, suggesting the involvement of this enzyme in the pathway that generates angiogenic activity. Neither of these substances directly inhibited the M phi-derived angiogenic activity. LPS-induced production of the cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 8 (IL-8) was not significantly reduced when M phi were incubated in the absence of L-arginine. Similarly, L-NMMA and L-NAME did not significantly reduce the LPS-induced production of these cytokines by M phi in the presence of L-arginine. These results suggest that the LPS-stimulation-dependent generation of angiogenic activity by M phi requires an L-arginine-dependent NO-synthase effector mechanism that may be independent of the generation of TNF-alpha and IL-8.
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PMID:Production of angiogenic activity by human monocytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism. 751 98

1. Recent studies have suggested that the generation of nitric oxide (NO) and hydrogen peroxide (H2O2) by islet NO synthase and monoamine oxidase, respectively, may have a regulatory influence on insulin secretory processes. We have investigated the pattern of insulin release from isolated islets of Langerhans in the presence of various pharmacological agents known to perturb the intracellular levels of NO and the oxidation state of SH-groups. 2. The NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) dose-dependently increased L-arginine-induced insulin release. D-Arginine did not influence L-arginine-induced insulin secretion. However, D-NAME which reportedly has no inhibitory action on NO synthase, modestly increased L-arginine-induced insulin release, but was less effective than L-NAME. High concentrations (10 mM) of D-arginine as well as L-NAME and D-NAME could enhance basal insulin release. 3. The intracellular NO donor, hydroxylamine, dose-dependently inhibited insulin secretion induced by L-arginine and L-arginine+L-NAME. 4. Glucose-induced insulin release was increased by NO synthase inhibition (L-NAME) and inhibited by the intracellular NO donor, hydroxylamine. Sydnonimine-1 (SIN-1), an extracellular donor of NO and superoxide, induced a modest suppression of glucose-stimulated insulin release. SIN-1 did not influence insulin secretion induced by L-arginine or the adenylate cyclase activator, forskolin. 5. The intracellular 'hydroperoxide donor' tert-butylhydroperoxide in the concentration range of 0.03-3 mM inhibited insulin release stimulated by the nutrient secretagogues glucose and L-arginine. Low concentrations (0.03-30 microM) of tert-butylhydroperoxide, however enhanced insulin secretion induced by the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX). 6. Islet guanosine 3':5'-cyclic monophosphate (cyclic GMP) content was not influenced by 10 mML-arginine or tert-butylhydroperoxide at 3 or 300 micro M but was markedly increased (14 fold) by a high hydroxylamine concentration (300 micro M). In contrast, islet adenosine 3':5'-cyclic monophosphate (cyclicAMP) content was increased (3 fold) by L-arginine (10 mM) and (2 fold) by tert-butylhydroperoxide(300 micro M).7. Our results strongly suggest that NO is a negative modulator of insulin release induced by the nutrient secretagogues L-arginine and glucose. This effect is probably not mediated to any major extent by the guanylate cyclase-cyclic GMP system but may rather be exerted by the S-nitrosylation of critical thiol groups involved in the secretory process. Similarly the inhibitory effect of tert-butylhydroperoxide is likely to be elicited through affecting critical thiol groups. The mechanism underlying the secretion promoting action of tert-butylhydroperoxide on IBMX-induced insulin release is probably linked to intracellular Ca2+-perturbations affecting exocytosis.8. Taken together with previous data the present results suggest that islet production of low physiological levels of free radicals such as NO and H202 may serve as important modulators of insulin secretory processes.
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PMID:Influence of nitric oxide synthase inhibition, nitric oxide and hydroperoxide on insulin release induced by various secretagogues. 753 13

1. Castor oil (2 ml orally) produced copious diarrhoea in rats 3 h after its administration. 2. Pretreatment (intraperitoneal, i.p.) of rats with the NO synthesis inhibitors NG-nitro-L-arginine methyl ester (L-NAME, 1-25 mg kg-1) and NG-monomethyl-L-arginine (L-NMMA, 2.5-100 mg kg-1) inhibited or prevented castor-oil-induced diarrhoea. L-Arginine (150-600 mg kg-1, i.p.) administered to rats pretreated with L-NAME 10 mg kg-1, drastically reduced the antidiarrhoeal activity of L-NAME in a dose-related manner. D-Arginine (900 mg kg-1) did not modify the protection by L-NAME. 3. Pretreatment (i.p.) of rats with L-NAME (2.5-25 mg kg-1) decreased the intestinal fluid accumulation and Na+ secretion induced by castor oil. L-Arginine (600 mg kg-1) but not D-arginine (900 mg kg-1) counteracted the inhibitory effect of L-NAME (10 mg kg-1). 4. L-NAME (10 and 25 mg kg-1) had no significant effect on the intestinal transit in normal rats or those given castor oil. 5. These results provide evidence that nitric oxide (NO) could play an important role in castor-oil-induced diarrhoea.
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PMID:Inhibitors of nitric oxide synthetase prevent castor-oil-induced diarrhoea in the rat. 768 65

L-Arginine is the biological precursor for nitric oxide (NO). NO is formed continuously in endothelial cells and maintains a certain degree of vasodilator tone under physiological conditions. Although the formation of NO is not primarily controlled by precursor availability, the extent to which extra supplementation with L-arginine may affect endothelial NO formation, and hence, vasodilator tone and systemic blood pressure, is not entirely clear. To address this issue, we infused L-arginine i.v. in anaesthetized normotensive rats pretreated with NG-nitro-L-arginine methyl ester (L-NAME, 50 or 200 mg-1) and in untreated controls, under continued recording of mean arterial pressure (MAP). In control animals L-arginine (25 or 100 mg kg-1 min-1) had no effect on systemic MAP (111 +/- 3 mm Hg), while L-arginine (200 mg kg-1 min-1) lowered MAP (to 70 +/- 6 mm Hg). D-Arginine (200 mg kg-1 min-1) also induced hypotension; during infusion of D-arginine MAP fell from 106 +/- 4 to 64 +/- 4 mm Hg. Pretreatment with L-NAME (50 and 200 mg kg-1) elevated MAP to 140 +/- 2 and 147 +/- 3 mm Hg, respectively, but failed to affect the hypotensive response to L-arginine; during infusion of L-arginine (200 mg kg-1 min-1) in rats pretreated with L-NAME (50 and 200 mg kg-1) MAP fell to 86 +/- 9 and 104 +/- 6 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:L-arginine-induced hypotension in the rat: evidence that NO synthesis is not involved. 770 39

1. The effects of inhibiting nitric oxide (NO)-synthase on fluid transport, mucosal cyclic GMP and cyclic AMP levels and intraluminal prostaglandin E2 (PGE2)-release were studied in a model of ligated jejunal loops of anaesthetized rats in vivo. Experiments were performed under basal conditions as well as under conditions, when net fluid secretion was induced by Escherichia coli heat stable enterotoxin a (E. coli STa) or PGE2. 2. Intravenous infusion of the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 0.25-50 mg kg-1, 45 min) dose-dependently reversed net fluid absorption to net secretion, whereas infusion of D-NAME, the inactive enantiomer of L-NAME, in corresponding doses did not influence net fluid transport. N omega-nitro-L-arginine (L-NOARG, 25 mg kg-1), another NO-synthase inhibitor, also elicited net secretion of fluid. 3. L-NAME (25 mg kg-1)-induced net fluid secretion was reversed to net absorption by infusion of L-arginine (400 mg kg-1) or sodium nitroprusside (1 mg kg-1) and s.c. administration of indomethacin (10 mg kg-1). Hexamethonium (1 mg kg-1, s.c.), a ganglionic blocker and granisetron (100 micrograms kg-1, s.c.), a 5-HT3-receptor antagonist, did not influence L-NAME-induced net secretion. 4. Net fluid secretion induced by intraluminal instillation of E. coli STa (10 units ml-1) was enhanced by infusion of L-NAME (25 mg kg-1) and was inhibited by infusion of L-arginine (400 mg kg-1) and sodium nitroprusside (1 mg kg-1). D-Arginine (400 mg kg-1) did not influence E. coli STa-induced fluid secretion. Likewise, net fluid secretion induced by i.a. infusion of PGE2 (79 ng ml-1, 30 min) was enhanced by infusion of L-NAME and was inhibited by L-arginine and sodium nitroprusside. D-Arginine(400 mg kg-1) did not influence PGE2-induced fluid secretion.5. PGE2 levels in intraluminal fluid were not elevated after infusion of L-NAME (25mgkg-1) compared to controls.6. Mucosal cyclic GMP and cyclic AMP levels after L-NAME-treatment were not different from control values.7. These results indicate that nitric oxide plays an important role in the regulation of intestinal fluid transport. The data suggest a nitric oxide-dependent proabsorptive tone in the intestine, which possibly involves the enteric nervous system and suppression of prostaglandin formation. This proabsorptive tone also may downregulate fluid secretion induced by E. coli STa or PGE2.
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PMID:Significance of nitric oxide in the stimulation of intestinal fluid absorption in the rat jejunum in vivo. 771 8

1. L-Arginine (100-1000 mg kg-1) administered orally (p.o.) or intraperitoneally (i.p.), but not intracerebroventricularly (i.c.v., 0.08 mg per mouse), reduced the antinociceptive effect of morphine (0.5-10 mg kg-1 s.c.) assessed in mice using three different tests: hot plate, tail-flick and acetic acid-induced writhing. D-Arginine (up to 1000 mg kg-1 p.o. or i.p.) was ineffective. 2. NG-Monomethyl-L-arginine (L-NMMA, 5-50 mg kg-1 i.p.) and NG-nitro-L-arginine methyl ester (L-NAME, 5- 30 mg kg-1 i.p.), but not NG-nitro-D-arginine methyl ester (D-NAME, 30 mg kg-1 i.p.), reversed in all assays the effect of L-arginine on morphine-induced antinociception. 3. Morphine (10 mg kg-1 s.c.), L-arginine (1000 mg kg-1 p.o.) or L-NAME (30 mg kg-1 i.p.), either alone or in combination, did not produce changes in locomotor activity or sensorimotor performance of animals. 4. These results suggest that the L-arginine-nitric oxide pathway plays a modulating role in the morphine-sensitive nociceptive processes.
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PMID:Modulation of morphine antinociception in the mouse by endogenous nitric oxide. 788 94


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