Nitric Oxide Produced by Inducible Nitric Oxide Synthase Delays Gastric Emptying in Lipopolysaccharide-treated Rats

Takakura, Ko; Hasegawa, Kôichi; Goto, Yukio; Muramatsu, Ikunobu

doi:10.1097/00000542-199709000-00027

Cited by 48 publications

(43 citation statements)

References 26 publications

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“…During late endotoxemia, iNOS inhibition also reversed, almost completely, the increase in gastric retention. This finding is consistent with a previous study in rats, in which iNOS inhibition with aminoguanidine (a selective iNOS inhibitor) administered 5 h after LPS administration partially reversed the delay in gastric emptying in late endotoxemia (2).…”

Section: Discussionsupporting

confidence: 93%

“…Endotoxemia, which occurs after lipopolysaccharide (LPS) injection, delays gastric emptying and disrupts intestinal transit (1)(2)(3)(4)(5)(6)(7). However, it is not clear whether the latter effect involves a delay or acceleration since both have been reported (1,(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…However, it is not clear whether the latter effect involves a delay or acceleration since both have been reported (1,(5)(6)(7). While uncertainties remain about the nature of the effect of LPS on gastrointestinal motility, the effect is suspected to involve various cytokines that are produced in response to LPS (1)(2)(3)(4)(5)(6)(7)(8). Intraperitoneal (ip) injection of LPS in mice elicits a surge in serum tumor necrosis factor-α (TNF-α) at 1-2 h, followed by an increase in serum interleukin-1ß (IL-1ß), and a subsequent increase in serum levels of IL-6 (5).…”

Section: Introductionmentioning

confidence: 99%

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Inducible nitric oxide synthase and tumor necrosis factor-alpha in delayed gastric emptying and gastrointestinal transit induced by lipopolysaccharide in mice

Inada¹,

Hamano²,

Yamada³

et al. 2006

Braz J Med Biol Res

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Gastrointestinal motility disturbances during endotoxemia are probably caused by lipopolysaccharide (LPS)-induced factors: candidates include nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß, and interleukin-6. Flow cytometry was used to determine the effects of LPS and these factors on gastric emptying (evaluated indirectly by determining percent gastric retention; %GR) and gastrointestinal transit (GIT) in male BALB/c mice (23-28 g). NO (300 µg/mouse, N = 8) and TNF-α (2 µg/mouse, N = 7) increased (P < 0.01) GR and delayed GIT, mimicking the effect of LPS (50 µg/mouse). During early endotoxemia (1.5 h after LPS), inhibition of inducible NO synthase (iNOS) by a selective inhibitor, 1400 W (150 µg/mouse, N = 11), but not antibody neutralization of TNF-α (200 µg/mouse, N = 11), reversed the increase of GR (%GR 78.8 ± 3.3 vs 47.2 ± 7.5%) and the delay of GIT (geometric center 3.7 ± 0.4 vs 5.6 ± 0.2). During late endotoxemia (8 h after LPS), both iNOS inhibition (N = 9) and TNF-α neutralization (N = 9) reversed the increase of GR (%GR 33.7 ± 2.0 vs 19.1 ± 2.6% (1400 W) and 20.1 ± 2.0% (anti-TNF-α)), but only TNF-α neutralization reversed the delay of GIT (geometric center 3.9 ± 0.4 vs 5.9 ± 0.2). These findings suggest that iNOS, but not TNF-α, is associated with delayed gastric emptying and GIT during early endotoxemia and that during late endotoxemia, both factors are associated with delayed gastric emptying, but only TNF-α is associated with delayed GIT. Correspondence

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inducible nitric oxide synthase and tumor necrosis factor-alpha in delayed gastric emptying and gastrointestinal transit induced by lipopolysaccharide in mice

Inada¹,

Hamano²,

Yamada³

et al. 2006

Braz J Med Biol Res

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“…The authors concluded that exogenous NO has a prejunctional inhibitory effect on the nitrergic component of the NANC response, resulting from a down-regulation of nNOS (De Man et al, 1995). Studies of the effect of the endotoxin lipopolysaccharide on the GI tract have associated delay in gastric emptying and intestinal transit with increased expression of inducible NOS (iNOS) (Takakura et al, 1997;Fan et al, 2001;De Winter et al, 2002). The substantial concentrations of NO which can be generated by iNOS are known to autoinhibit the constitutive forms of NOS (cNOS), which may result in a condition in which iNOS is overexpressed, while cNOS is concurrently inhibited (Schwartz et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Chronic Alcohol Consumption Affects Gastrointestinal Motility and Reduces the Proportion of Neuronal NOS‐Immunoreactive Myenteric Neurons in the Murine Jejunum

Bagyánszki

Krecsmarik

Winter

et al. 2010

The Anatomical Record

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Alcohol consumption interferes with gastrointestinal transit causing symptoms in alcoholic patients. Nitric oxide (NO), synthesized by neuronal nitric oxide synthase (nNOS) plays an important role in the control of gastrointestinal motility. Our aim was to investigate whether chronic alcohol intake in a murine model induces gastrointestinal motility disturbances and affects the nitrergic myenteric neurons in the stomach and jejunum. Gastric emptying, small intestinal transit and geometric centre were measured in vivo after intragastric gavage of Evans blue. Nitrergic relaxations to electrical field stimulation (EFS) and exogenous NO were recorded in jejunal muscle strips in vitro. The proportion of nNOS-immunopositive myenteric neurons was assessed using PGP9.5 and nNOS immunostaining. After chronic alcohol consumption, gastric emptying and small intestinal transit were delayed compared with control mice, and the nitrergic nervemediated relaxations to EFS in the jejunum were decreased, whereas relaxations to exogenous NO did not differ. The proportion of nNOS-immunoreactive neurons did not change in the stomach, whereas in the jejunum the percentage decreased from 33% to 27% (P < 0.001) after chronic alcohol intake. The total number of myenteric neurons remained unchanged. These results suggest that chronic alcohol consumption disturbs gastric and small intestinal motility in vivo and in vitro and is associated with a decrease in the proportion of nNOS-immunoreactive myenteric neurons in the murine jejunum. Anat Rec, 293:1536Rec, 293: -1542Rec, 293: , 2010.

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“…Doses of endotoxin that do not modify systemic arterial blood pressure or rectal temperature selectively decrease gastric acid secretion (Barrachina et al 1995a;Esplugues et al 1996;Martínez-Cuesta et al 1994), increase the mucosal resistance to damage (Barrachina et al 1995b) and decrease gastric emptying of non-nutrient, usually liquid, meals (Collares 1997;Cullen et al 1995;Takakura et al 1997;van Miert and de la Parra 1970). These effects of endotoxin do not appear to be the consequence of a local mechanism and seem to be mediated by reflex pathways involving extrinsic innervation of the gut.…”

Section: Introductionmentioning

confidence: 99%

Endotoxin inhibits gastric emptying in rats via a capsaicin-sensitive afferent pathway

Calatayud

Barrachina

García-Zaragozá

et al. 2001

Naunyn-Schmiedeberg's Archives of Pharmacology

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The effects of endotoxin on gastric emptying of a solid nutrient meal and the neural mechanisms involved in such a response were investigated in conscious rats. The intraperitoneal (i.p.) administration of E. coli endotoxin (40 microg/kg) significantly reduced the 4-h rate of gastric emptying of a standard solid nutrient meal. Ablation of primary afferent neurons by systemic administration of high doses of capsaicin (20+30+50 mg/kg s.c.) to adult rats did not modify the rate of gastric emptying in control animals but prevented the delay in gastric transit induced by endotoxin. Local application of capsaicin to the vagus nerve rather than application of capsaicin to the celiac ganglion significantly repressed endotoxin-induced delay in gastric emptying. Neither treatment modified the rate of gastric emptying in vehicle-treated animals. Blockade of CGRP receptors (CGRP 8-37, 100 microg/kg i.v.) did not alter gastric emptying in control animals but significantly prevented endotoxin-induced inhibition of gastric emptying. In contrast, a tachykinin receptor antagonist ([D-Pro2, D-Trp7.9]-substance P, 2 mg/kg i.p.) significantly reduced the rate of gastric emptying in control animals and did not modify the inhibitory effects of endotoxin. Adrenergic blockade with phentolamine (3 mg/kg i.p.) +/- propranolol (5 mg/kg i.p.) or muscarinic antagonism with atropine (0.1 mg/kg i.p.) failed to reverse the delay in gastric emptying induced by endotoxin. These observations indicate that endotoxin-induced delay in gastric emptying of a solid nutrient meal is mediated by capsaicin-sensitive afferent neurons.

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Nitric Oxide Produced by Inducible Nitric Oxide Synthase Delays Gastric Emptying in Lipopolysaccharide-treated Rats

Abstract: The present study suggests that NO, probably produced by iNOS, is one of the factors involved in the delay of gastric emptying in the LPS-treated rats and probably in those with sepsis.

Cited by 48 publications

References 26 publications

Inducible nitric oxide synthase and tumor necrosis factor-alpha in delayed gastric emptying and gastrointestinal transit induced by lipopolysaccharide in mice

Inducible nitric oxide synthase and tumor necrosis factor-alpha in delayed gastric emptying and gastrointestinal transit induced by lipopolysaccharide in mice

Chronic Alcohol Consumption Affects Gastrointestinal Motility and Reduces the Proportion of Neuronal NOS‐Immunoreactive Myenteric Neurons in the Murine Jejunum

Endotoxin inhibits gastric emptying in rats via a capsaicin-sensitive afferent pathway

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