The role of endogenous nitric oxide and platelet-activating factor in hypoxia-induced intestinal injury in rats

Caplan, Michael S.; Hedlund, Erik; Hill, Nicole; MacKendrick, William

doi:10.1016/0016-5085(94)90591-6

Cited by 92 publications

(40 citation statements)

References 21 publications

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“…These discrepancies could be due to differences in either experimental conditions or properties of the tissues studied, which differ in both cellular components and vascularity. In keeping with the difficulty of assigning a damaging role to NO production in tissue injury there are a number of reports emphasizing its role as an oxygen radical scavenger (Wink et al, 1993;Choi, 1993), and its protective role in hypoxia-induced intestinal injury in rats (Caplan et al, 1994). Alternative roles for NO in immunemediated inflammation could be regulation of blood flow in the reparative phase of inflammation (Moncada et al, 1991;Pons et al, 1993), or reduction of leukocyte adherence and emigration after the initial injury (Arndt et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Platelet‐activating factor: the effector of protein‐rich plasma extravasation and nitric oxide synthase induction in rat immune complex peritonitis

Steil¹,

Garcia‐Rodriguez²,

Crespo³

1995

British J Pharmacology

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1 The involvement of platelet-activating factor (PAF) in immune complex-induced/polymorphonuclearmediated tissue injury was studied by use of a reverse passive Arthus (RPA) model in the peritoneal cavity of rats. 2 Extravasation of protein-rich plasma, accumulation of polymorphonuclear leukocytes (PMN), and the production of nitric oxide (NO) by resident peritoneal mononuclear phagocytes were assayed. 3 Treatment of rats with either UR-12460 or BB-823, two compounds which possess different chemical structures, but elicit the same antagonistic effect on the PAF receptor, abrogated protein-rich plasma extravasation. In contrast, they did not show any effect on the accumulation of PMN. 4 Inhibition of NO production with both N1-mono methyl-L-arginine and N0-nitro-L-arginine failed to prevent protein-rich plasma extravasation. 5 The production of NO by peritoneal adherent cells following RPA was measured in cells maintained for 2 to 28 h in culture, and it was significantly increased in cells removed as early as 15 min after RPA induction, as compared to controls. 6 Addition of 10 nM PAF to the culture medium reduced the generation of NO by peritoneal cells from RPA rats, whereas this mediator enhanced NO production in cells from naive control animals. 7 Treatment with either UR-12460 or BB-823 prior to the induction of RPA produced an almost complete inhibition of NO production. 8 Assay of nitric oxide synthase activity in cell homogenates from peritoneal cells showed that the activity was due to the inducible form of the enzyme. 9 Study by Northen blotting of mRNA coding for the inducible NO synthase (iNOS) showed transcription at 6 and 18 h after the induction of RPA, which was inhibited in UR-12460-treated rats. 10 These data indicate that PAF is the main mediator of the early plasma leakage observed in RPA, and also that PAF is implicated in the triggering of long-term changes via induction of specific genes, as judged from its ability to promote the expression of iNOS.

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Section: Discussionmentioning

confidence: 99%

Platelet‐activating factor: the effector of protein‐rich plasma extravasation and nitric oxide synthase induction in rat immune complex peritonitis

Steil¹,

Garcia‐Rodriguez²,

Crespo³

1995

British J Pharmacology

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“…These include inducing hypoxia for 5 min followed by 10 min with 100% oxygen [133] , hypoxia for 50 s followed by cold exposure [134] , superior mysenteric artery clamping with or without PAF [135] , intraarterial injection of TNF-α [136] , and placing rats into a 100% nitrogen or 10% oxygen environment [24] . Finally, a rat model has been described by Chan [137] who created intestinal ischemia by increasing intraluminal pressure and injecting E. coli into the lumen.…”

Section: Nec Modelsmentioning

confidence: 99%

Necrotizing enterocolitis: A multifactorial disease with no cure

Schnabl

Aerde²,

Thomson³

et al. 2008

WJG

163

120

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INTRODUCTIONNecrotizing enterocolitis (NEC) is an inflammatory bowel disease of neonates and remains one of the most common gastrointestinal emergencies in newborn infants [1] . Onset of NEC is often within the first three months of life and neonates who are of extremely low birth weight (< 1000 g) and under 28 wk gestation are the most susceptible [2] . Full term neonates account for 10% of all NEC cases while premature infants account for 90% [3] . With an incidence rate of 1%-5% for all newborns admitted to the NICU [1] , a prevalence of 7%-14% of very low birth weight infants (VLBW, 500-1500 g) [4] and a mortality rate approaching 20%-50% [5] , NEC continues to represent a significant clinical problem. In Canada, the incidence rate is 1.8 per 100 live births with a prevalence of 7% of VLBW infants [1] . Advances in obstetric and neonatal care have improved survival rates for smaller, more immature infants, and as more VLBW preterm infants survive the neonatal period, the population at risk for NEC increases [1] .No consistent association between sex, race, and rates of NEC has been identified. However, male VLBW infants and black infants are at greater risk of death [6] . Due to inadequate treatments and no effective preventative strategy, an estimated 20%-40% of babies with NEC require surgery [1] and 10%-30% experience significant morbidity including neurodevelopmental impairment, vision and hearing impairment, failure to thrive, feeding abnormalities, diarrhea, bowel obstruction, and short bowel syndrome [1,2,7] . The case fatality rate with surgical intervention is as high as 50% [1] . NEC is also a financial burden to the health care system with yearly hospital charges reported to be as high as $6.5 million in the US [8] . Thus, NEC continues to be an important health issue for preterm neonates. DIAGNOSIS Clinical signs and symptomsThe onset of NEC can occur suddenly within a few AbstractNecrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature of the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events, formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear. Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Development of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

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“…In addition, Werner et al [15] reported that L-arginine, as well as the NO donor sodium nitroprusside, reduced inflammation in rats with caerulein-induced pancreatitis. Beneficial effects of L-arginine treatment have also been observed in experimental models of other disease states, including hypoxia-induced intestinal injury [27] and reperfusioninduced mucosal barrier dysfunction [28].…”

Section: Discussionmentioning

confidence: 99%

“…In feline models of intestinal ischemia and reperfusion, the nitric oxide (NO) donors L-arginine, nitroprusside, spermine NO, and 3-morpholinosydonimine-N-ethyl-carbamide (SIN1) all attenuated increases in intestinal permeability and reperfusion-induced mucosal barrier dysfunction [29,30]. In a rat model of hypoxiainduced intestinal ischemia, hypoxia plus treatment with the NO synthase inhibitor NG-methyl-L-arginine [LNMA] led to intestinal injury, which was prevented with exogenous L-arginine [28]. However, treatment with the NO synthase inhibitor L-NAME ameliorated an endotoxin-induced increase in intestinal mucosal permeability in another study [31].…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide regulates bacterial translocation in experimental acute edematous pancreatitis

et al. 2003

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The role of endogenous nitric oxide and platelet-activating factor in hypoxia-induced intestinal injury in rats

Cited by 92 publications

References 21 publications

Platelet‐activating factor: the effector of protein‐rich plasma extravasation and nitric oxide synthase induction in rat immune complex peritonitis

Platelet‐activating factor: the effector of protein‐rich plasma extravasation and nitric oxide synthase induction in rat immune complex peritonitis

Necrotizing enterocolitis: A multifactorial disease with no cure

Nitric oxide regulates bacterial translocation in experimental acute edematous pancreatitis

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