Downregulation of nNOS and synthesis of PGs associated  with endotoxin-induced delay in gastric emptying

Calatayud, Sara; García-Zaragozá, Eugenia; Hernández, Carlos; Quintana, Elsa; Felipo, Vicente; Esplugues, Juan V.; Barrachina, M D

doi:10.1152/ajpgi.00168.2002

Cited by 56 publications

(51 citation statements)

References 36 publications

(42 reference statements)

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“…At 8 h after LPS, iNOS was expressed in the intestine, whereas nNOS expression became undetectable (Figure 2). These findings are consistent with previous reports showing that iNOS expression is induced and nNOS expression is down-regulated by LPS treatment (17,18), demonstrating the efficacy of endotoxemia induction in our study.…”

Section: Efficacy Of Lps Treatmentsupporting

confidence: 94%

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: Efficacy Of Lps Treatmentsupporting

confidence: 94%

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 neuronal nitric oxide synthase gene (nNOS) is located within 8 centimorgans of the putative cholesterol absorption locus on chromosome 5. Gastric emptying has been reported to be significantly delayed in nNOS knockout mice, and chronic depletion of nitric oxide by nitric oxide synthase (NOS) inactivation results in delayed gastric emptying (33,53,54). In the current study, inhibition of NOS also resulted in delayed gastric emptying with a concomitant increase of cholesterol absorption in SJL/J mice.…”

Section: Discussionmentioning

confidence: 99%

Rate of gastric emptying influences dietary cholesterol absorption efficiency in selected inbred strains of mice

Kirby

Howles

Hui

2004

Journal of Lipid Research

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Dietary cholesterol contributes ‫ف‬ 50% of the circulating cholesterol in humans and ‫ف‬ 30% of the circulating cholesterol in mice (1, 2). Despite the importance of this process in determining plasma cholesterol level, the mechanisms dictating dietary cholesterol absorption efficiency have not been completely elucidated. This incomplete information is attributable in part to the complexity of the cholesterol absorption process, which involves lipid emulsification in the stomach, lipolytic digestion and bile salt solubilization in the intestinal lumen, enterocyte uptake of the dietary cholesterol, and its assembly into lipoproteins before secretion into the circulation. Thus, differences in the rate and efficiency of each of these processes will contribute to variations in cholesterol absorption efficiency among different individuals.Cholesterol absorption efficiency in humans varies among different individuals even though they may be consuming a similar diet (3-6). Individual differences in cholesterol absorption efficiency were also observed among various inbred strains of rabbits (7,8), rats (9), and mice (10-15). These results suggested a genetic component in the regulation of cholesterol absorption. Early studies on the identification of cholesterol absorption genes have focused on enzymes important for cholesterol ester metabolism in the gastrointestinal tract. Studies with gene knockout mice and specific enzyme inhibitors revealed that both the cholesterol esterification enzyme acyl-CoA:cholesterol acyltransferase and the cholesterol ester hydrolytic enzyme cholesterol esterase modulate the type of intestinal lipoproteins produced (16,17). However, both of these enzymes play only minor roles in determining cholesterol absorption efficiency under normal dietary conditions (16-20). In contrast, enzymes that modulate cholesterol solubility in the intestinal lumen, such as the bile acid synthetic enzymes cholesterol 7 ␣ -hydrolase and sterol 27-hydroxylase, impact cholesterol absorption indirectly by modulating the physical structure of the cholesterol carrier in the intestinal lumen (21,22). More recently, the ATP binding cassette transporter proteins, including ABCA1, ABCG5, and ABCG8, have been implicated as important regulators of dietary cholesterol absorption. These transporters may limit the amount of cholesterol absorbed by enterocytes by catalyzing cholesterol efflux to the intestinal lumen (23-26).Abbreviations: LCT, long-chain triglyceride; l -NAME, N -nitro-l -arginine; MCT, medium-chain triglyceride.

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“…The primers used are summarized in Table 1. The primer pairs specific for eNOS, inducible-type NOS (iNOS), and neuronal-type NOS (nNOS) were selected by analysis of the published cDNA sequences (7,31,46). PCR cycles (94°C for 1 min, 56 -64°C for 1 min, 72°C for 1 min) were performed with one-half of the reverse transcription mixture.…”

Section: Measurement Of Expression Of Mrnas For ␣2d- ␣1b- and ␣1d-amentioning

confidence: 99%

Differential expression of α_2D-adrenoceptor and eNOS in aortas from early and later stages of diabetes in Goto-Kakizaki rats

Kobayashi¹,

Matsumoto²,

Ooishi³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Kobayashi, Tsuneo, Takayuki Matsumoto, Kazuyuki Ooishi, and Katsuo Kamata. Differential expression of ␣2D-adrenoceptor and eNOS in aortas from early and later stages of diabetes in Goto-Kakizaki rats. Am J Physiol Heart Circ Physiol 287: H135-H143, 2004; 10.1152/ajpheart.01074.2003.-The aim of the present study was to compare vascular dysfunction between the early (12 wk old) and later (36 wk old) stages of spontaneous diabetes in GotoKakizaki (GK) rats. We also evaluated the aortic expression of the ␣2D-adrenoceptor and endothelial nitric oxide synthase (eNOS). Vascular reactivity was assessed in thoracic aortas from age-matched control rats and 12-and 36-wk GK rats. Using RT-PCR and immunoblots, we also examined the changes in expression of the ␣2D-adrenoceptor and eNOS. In aortas from GK rats (vs. those from age-matched control rats): 1) the relaxation response to ACh was enhanced at 12 wk but decreased at 36 wk; 2) the relaxation response to sodium nitroprusside was decreased at both 12 and 36 wk, 3) norepinephrine (NE)-induced contractility was decreased at 12 wk but not at 36 wk, 4) the expressions of ␣1B-and ␣1D-adrenoceptors were unaffected, whereas those of ␣2D-adrenoceptor and eNOS mRNAs were increased at both 12 and 36 wk; and 5) NE-and ACh-stimulated NOx (nitrite and nitrate) levels were increased at 12 wk, although at 36 wk ACh-stimulated NOx was lower, whereas NE-stimulated NOx showed no change. These results clearly demonstrate that enhanced ACh-induced relaxation and impaired NE-induced contraction, due to NO overproduction via eNOS and increased ␣2D-adrenoceptor expression, occur in early-stage GK rats and that the impaired AChinduced relaxation in later-stage GK rats is due to reductions in both NO production and NO responsiveness (but not in eNOS expression).Type 2 diabetes; ␣2D-adrenoceptor; endothelium; nitric oxide synthase; relaxation DIABETES MELLITUS is an important risk factor for the development of atherosclerosis. Numerous epidemiological studies have indicated that the insulin resistance and hyperinsulinemia associated with Type 2 diabetes make important contributions to the development of hypertension and atherosclerotic lesions. Although an accumulating body of evidence indicates that endothelium-dependent relaxation is weaker both in a Type 1 diabetic model, namely, streptozotocin (STZ)-induced diabetic rats (11, 26, 32, 39 -41), and in Type 2 diabetic rats (28, 44, 50, 51), we (29) and others (6, 42) have noted an augmented or unaltered endothelium-dependent relaxation at an early stage in STZ-induced diabetes. In fact, there is clinical and experimental evidence of augmented blood flow at early stages of diabetes (9, 24). In the Type 1 model STZ-induced diabetic rat, Pieper (42) showed that there is an early (for 1 day) increase in endothelium-dependent relaxation, followed by a reversion phase (for 1-2 wk), in which relaxation is normal, and then a final phase (for 8 wk) of impaired relaxation. In a Type 2 model, the obese Zucker rat, the aorta has been reported to exhibit eith...

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Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying

Cited by 56 publications

References 36 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

Rate of gastric emptying influences dietary cholesterol absorption efficiency in selected inbred strains of mice

Differential expression of α_2D-adrenoceptor and eNOS in aortas from early and later stages of diabetes in Goto-Kakizaki rats

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Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying

Cited by 56 publications

References 36 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

Rate of gastric emptying influences dietary cholesterol absorption efficiency in selected inbred strains of mice

Differential expression of α2D-adrenoceptor and eNOS in aortas from early and later stages of diabetes in Goto-Kakizaki rats

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Differential expression of α_2D-adrenoceptor and eNOS in aortas from early and later stages of diabetes in Goto-Kakizaki rats