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)

To investigate the contribution of nitric oxide in the regulation of regional blood flow and metabolism in vivo, we administered incremental doses of N omega-L-arginine-methyl ester (L-NAME 1, 3, 10, 30 and 100 mg kg-1, intravenously) in isoflurane anaesthetized pigs. The pulmonary vascular bed exhibited a greater sensitivity to the L-NAME-induced pressor effects compared with the systemic arterial bed as the slope of the dose-response curve was steeper (42.9 +/- 4.3 vs. 24.3 +/- 3.6, P < 0.05) and the dose of L-NAME required to induce a 25% pressure increase was lower (PD25 of 6.2 +/- 2.5 vs. 22.8 +/- 5.2 mg kg-1, P < 0.05). L-NAME infusion produced a dose-dependent reduction in cardiac output that was evenly distributed among the mesenteric, femoral, hepatic and carotid arterial circulation as demonstrated by unchanged regional blood flows-to-cardiac output ratios, except in the kidney where the L-NAME-induced vasoconstriction was most pronounced (renal blood flow/cardiac output decreased from 6.2 +/- 0.6 to 3.7 +/- 0.7% after 100 mg kg-1 of L-NAME, P < 0.05). After the administration of L-NAME 30 mg kg-1, intestinal O2 uptake (Vo2) increased (+39 +/- 3%, P < 0.05) whereas renal Vo2 tended to decrease (-19 +/- 4%, P = 0.07) and whole body Vo2 remained unchanged. Plasma noradrenaline and adrenaline concentrations did not change significantly with L-NAME infusion. These data demonstrate that in anaesthetized pigs, endogenous nitric oxide is most important for the regulation of pulmonary and renal blood flows and in spite of unchanged global metabolic demand, nitric oxide inhibition leads to an increase in intestinal Vo2 associated with enhanced gut motility without rise in circulating lactate levels.
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PMID:Role of nitric oxide in the regulation of regional blood flow and metabolism in anaesthetized pigs. 978 77

Our studies of fasted anesthetized rats have shown that all spontaneous relaxations of the antrum are nitric oxide (NO) dependent. Duodenal motility is patterned into propagating "grouped" motor activity interposed with "intergroup" periods of nonpropagating motor activity; in the duodenum, only intergroup relaxations are NO dependent. We examined the involvement of NO and ATP in spontaneous motor activities of the gastroduodenum in vivo: contractions and relaxations were recorded and analyzed simultaneously from the antrum (S1) and proximal duodenum (D1) of anesthetized Sprague-Dawley rats (n = 10/group), using extraluminal foil strain gauges. Treatment with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg iv) attenuated (P < 0.05) antral and intergroup relaxations, whereas grouped relaxations were enhanced (P < 0.05). These effects were reversed with L-arginine (300 mg/kg iv). L-NAME also increased (P < 0.05) the amplitude of duodenal contractions. ATP (8 mg. kg-1. min-1 iv) stimulated relaxations at S1 and D1 that were blocked by the P2-purinoceptor antagonist suramin (60 mg/kg iv). This treatment did not affect spontaneous antral relaxations; however, duodenal grouped relaxations were attenuated. Desensitization to the P2x-purinoceptor agonist alpha,beta-methylene ATP (300 micrograms/kg iv) gave results similar to suramin. In contrast, the P2y-purinoceptor agonist 2-methylthio-ATP (2-MeS-ATP; 360 micrograms/kg iv) evoked duodenal relaxations that were attenuated by L-NAME, and desensitization to 2-MeS-ATP attenuated intergroup relaxations. Spontaneous relaxations of the rat antrum and duodenal intergroup relaxations are NO dependent. Both gut regions relax in response to systemically administered ATP; this response is sensitive to suramin. Grouped duodenal relaxations display functional sensitivity to suramin and P2x- purinoceptor desensitization, indicative of the involvement of ATP and P2x purinoceptors. P2y purinoceptors must also be present; however, these occur on elements releasing NO. Although NO does not mediate grouped relaxations or duodenal contractions, the sensitivity of these responses to L-NAME indicates that the pathway(s) controlling these responses is modulated by NO.
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PMID:Rat gastroduodenal motility in vivo: involvement of NO and ATP in spontaneous motor activity. 981 16

Duodenal fat such as oleate is known to influence gut functions by release of cholecystokinin (CCK), but the contribution of CCK endogenously released by duodenal fat or by diversion of pancreatic juice from the duodenum in the mechanism of mucosal integrity and gastroprotection has been little studied. This study was designed to compare the effect of CCK-8 and intraduodenal (i.d.) instillation of sodium oleate, or diversion of the pancreatic biliary secretions that are known to release CCK, on the gastric mucosal lesions induced by topical application of 100% ethanol or acidified aspirin (ASA) in rats with or without the pretreatment with a CCK-A receptor antagonist, loxiglumide, or with L-365,260 to block CCK-B receptors. In addition, the effect of suppression of prostaglandin (PG) biosynthesis by indomethacin (5 mg/kg i.p.), inhibition of nitric oxide (NO)-synthase by L-NAME (5 mg/kg i.v.), or blockade of sensory nerves by capsaicin (125 mg/kg s.c.) on the protective activity of sodium oleate was determined. Sodium oleate (50-200 mM i.d.), or diversion of pancreatic juice from the duodenum for 3 h that produced significant rise in plasma CCK levels, significantly reduced gastric lesions induced by 100% ethanol to an extent similar to that induced by exogenous CCK-8 (5 nmol/kg s.c.). The protective effect of oleate or diversion of pancreatic juice was accompanied by an increase in gastric blood flow (GBF). Both protection and accompanying hyperemia were completely abolished by blockade of CCK-A receptors with loxiglumide, whereas L-365,260, an antagonist of CCK-B receptors, had no effect. Oleate given i.d. significantly attenuated acidified ASA-induced gastric lesions and gastric secretion while increasing the luminal concentration of somatostatin. These effects were significantly reduced by loxiglumide but not by L-365,260. In contrast, CCK-8, which stimulated gastric acid secretion, failed to affect the lesions induced by acidified ASA and the decrease in the GBF produced by this ulcerogen. Indomethacin, which suppressed PG generation by approximately 90%, failed to influence the protective activity of oleate or CCK-8 against ethanol-induced lesions, whereas L-NAME, vagotomy, or sensory denervation significantly attenuated this protection and accompanying hyperemia. Addition to L-NAME of L-arginine, but not D-arginine, restored the protective and hyperemic effects of CCK-8 and duodenal oleate against gastric lesions induced by ethanol or acidified ASA. We conclude that endogenous CCK released by oleate or diversion of pancreatic secretion exerts a potent gastroprotective action on the stomach involving predominantly CCK-A receptors and depending on vagal activity, and hyperemia mediated by NO and sensory nerves but unrelated to acid secretory effects and endogenous PG.
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PMID:Involvement of endogenous cholecystokinin and somatostatin in gastroprotection induced by intraduodenal fat. 987 9

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

Nitric oxide (NO) is a cotransmitter of inhibitory motor neurons of the enteric nervous system. This study examined the effect of 7-nitroindazole (7-NI), an inhibitor of neuronal NO synthase (NOS), on intestinal peristalsis and muscle activity and compared 7-NI with N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective inhibitor of NOS isoforms. Peristalsis in isolated segments of the guinea pig small intestine was triggered by a perfusion-induced rise of the intraluminal pressure. While L-NAME (10-300 micromol/l) lowered the peristaltic pressure threshold (PPT) at which propulsive muscle contractions were elicited, 7-NI (10-300 micromol/l) caused a concentration-related increase in PPT. L-Arginine (1-3 mmol/l) failed to reverse peristaltic motor depression evoked by 7-NI but annulled the L-NAME-evoked stimulation of peristalsis. Drugs which stimulated peristalsis, such as L-NAME, naloxone, apamin and suramin plus pyridoxal phosphate-6-azophenyl-2'-4'-disulphonic acid counteracted the inhibitory effect of submaximally effective concentrations of 7-NI on peristalsis. 7-NI (100-300 micromol/l) inhibited circular muscle contractions evoked by cholecystokinin octapeptide, the NK(1) receptor agonist GR-73,632 and indomethacin whereas L-NAME (100-300 micromol/l) failed to inhibit any drug-evoked contraction. These data show that 7-NI, unlike L-NAME, inhibits circular muscle contractions of the gut and depresses intestinal peristalsis. It is concluded that the inhibitory motor action of 7-NI is unrelated to inhibition of neuronal NOS and arises from depression of smooth muscle activity.
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PMID:Intestinal motor depression by 7-nitroindazole through an action unrelated to nitric oxide synthase inhibition. 1057 25

Nitric oxide (NO) in the gut has attracted increasing interest as a regulatory factor for a wide variety of intestinal functions. This study was performed to evaluate some methodological aspects and jejunal sources for NO synthesis. Bench side evaluations and an animal model using chloralose-anaesthetized pigs were used. Immunohistochemistry was performed on samples from pig intestine and direct measurements of intestinal NO formation were performed using intraluminal tonometry. Tonometric measurements were quantitatively accurate and with high reproducibility. A substantial NO formation was assessed which was markedly inhibited by luminal administration of the non-selective NOS inhibitor L-NAME. Intravenous administration of L-NAME also reduced jejunal NO formation but to a lesser extent. Immunohistochemistry revealed staining for the inducible type of NOS in the mucosal surface epithelium whereas endothelial and neuronal subtypes were located in deeper layers of the jejunal wall. The study argues for that the source of jejunal NO production, as measured by intraluminal tonometry, is located in close proximity with the intestinal mucosa. The NOS in this compartment is predominantly of the inducible type.
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PMID:Tonometric assessment of jejunal mucosal nitric oxide formation in anaesthetized pigs. 1075 9

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200-300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early N(G)-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI.
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PMID:Effect of N(G)-nitro-L-arginine methyl ester on intestinal permeability following intestinal ischemia-reperfusion injury in a rat model. 1147 51

High concentrations of nitric oxide (NO) produced by the inducible nitric-oxide synthase (iNOS) are associated with ulcerative inflammation and disease activity in colitis. Therefore, inhibition of iNOS serves as a novel experimental approach to treat gut inflammation. The aim of the present study was to investigate the effects of a novel highly selective iNOS inhibitor, N-[3-(aminomethyl)benzyl]acetamidine (1400W), as compared with a nonselective NOS inhibitor, N(G)-nitro-L-arginine-methyl-ester (L-NAME), in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis in the rat. Increased expression of iNOS protein and mRNA was found in acute TNBS-induced colitis along with neutrophil infiltration, inflammatory edema, and tissue damage. In a 24-h model of acute colitis, subcutaneous injections of 1400W (5 or 10 mg/kg t.i.d.) produced a 56 and 95% reduction in inflammatory edema formation, a 68 and 63% reduction in neutrophil infiltration (measured as myeloperoxidase activity), and a 19 and 26% decrease in the size of mucosal lesions as compared with vehicle treatment. Administration of L-NAME (35 mg/kg) failed to produce any significant beneficial effects as compared with vehicle treatment in this experimental model of acute colitis. Treatment with 1400W, a highly selective inhibitor of iNOS, reduced formation of edema, neutrophil infiltration, and macroscopic inflammatory damage in experimentally induced acute colitis in the rat. In contrast, nonselective nitric-oxide synthase inhibition with L-NAME provided no benefit. These results support the idea that selective iNOS inhibitors have a promise in the treatment of colitis.
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PMID:Suppression of acute experimental colitis by a highly selective inducible nitric-oxide synthase inhibitor, N-[3-(aminomethyl)benzyl]acetamidine. 1150 10

Nitric oxide (NO) signaling repressively regulates metamorphosis in two solitary ascidians and a gastropod. We present evidence for a similar role in the sea urchin Lytechinus pictus. NO commonly signals via soluble guanylyl cyclase (sGC). Nitric oxide synthase (NOS) activity in some mammalian cells, including neurons, depends on the molecular chaperone heat shock protein 90 (HSP90); this may be so in echinoid larvae as well. Pluteus larvae containing juvenile rudiments were treated with either radicicol L- or D-nitroarginine-methyl-ester (L-NAME and D-NAME), or IH-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), inhibitors of HSP90, NOS, and sGC, respectively. In all instances, drug treatment significantly increased the frequency of metamorphosis. SNAP, a NO donor, suppressed the inductive properties of L-NAME and biofilm, a natural inducer of metamorphosis. NADPH diaphorase histochemistry indicated NOS activity in cells in the lower lip of the larval mouth, the preoral hood, the gut, and in the tube feet of the echinus rudiment. Histochemical staining coincided with NOS immunostaining. Microsurgical removal of the oral hood or the pre-oral hood did not induce metamorphosis, but larvae lacking these structures retained the capacity to metamorphose in response to ODQ. We propose that the production of NO repressively regulates the initiation of metamorphosis and that a sensory response to environmental cues reduces the production of NO, and consequently cGMP, to initiate metamorphosis.
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PMID:NO/cGMP signaling and HSP90 activity represses metamorphosis in the sea urchin Lytechinus pictus. 1175 Dec 51

The distribution and possible effects on gastrointestinal motility of pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP), nitric oxide and gamma-amino-butyric acid (GABA) were investigated in the African clawed frog (Xenopus laevis) using immunohistochemistry and in vitro strip preparations. PACAP- and VIP-immunoreactive nerve fibres were common in the myenteric plexus as well as in the longitudinal and circular muscle layers all along the gastrointestinal tract. Double labelling demonstrated a close correlation between PACAP and VIP immunoreactivities, indicating that the two neurotransmitters are colocalised within the enteric nervous system. Occasionally, PACAP- and VIP-positive nerve cell bodies were seen in the myenteric or submucous plexa. In addition, VIP immunoreactivity coexisted with helospectin immunoreactivity. Nitric oxide synthase (NOS)-immunoreactive nerve cells were found in the myenteric plexus at an average density for the whole gastrointestinal tract of 4584 +/- 540 cells cm(-2). The NOS-immunoreactive nerve cells were usually multipolar with an average size of 11.3 +/- 3.7 x 23.2 +/- 6.6 microm. Some NOS-immunoreactive nerve fibres were VIP-immunoreactive but not all VIP-positive fibres showed NOS immunoreactivity. GABA immunoreactivity was found in nerve fibres and nerve cells in the myenteric plexus of all regions of the gut. Few GABA-immunoreactive nerve fibres were VIP-immunoreactive. PACAP 27, VIP, sodium nitroprusside (a nitric oxide donor; NaNP) and GABA caused similar responses on spontaneously contracting circular preparations of the cardiac stomach of X. laevis. The mean force developed was decreased, mainly by a reduction in resting tension, while the amplitude of contractions was not necessarily affected. The NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) increased the mean force developed, indicating a nitrergic tone in the preparations. In contrast, PACAP 27, VIP, NaNP, GABA and L-NAME had no significant effect on longitudinal strip preparations from the duodenum. These results indicate that PACAP, VIP, nitric oxide and GABA, which are known to be important inhibitory neurotransmitters in other vertebrates, are widely spread in the enteric nervous system of Xenopus laevis and may be involved in the inhibitory control of gastric motility. Although no effect of PACAP, VIP, nitric oxide or GABA on the longitudinal strips of the duodenum was seen in this study, this does not rule out the possibility that they might play an important role in controlling intestinal motility as well.
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PMID:Distribution and effects of PACAP, VIP, nitric oxide and GABA in the gut of the African clawed frog Xenopus laevis. 1191 71


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