Role of endogenous nitric oxide synthase inhibitor in gastric mucosal injury

2008 ◽  
Vol 86 (3) ◽  
pp. 97-104 ◽  
Author(s):  
Li Wang ◽  
Yuan Zhou ◽  
Jun Peng ◽  
Zhe Zhang ◽  
De-Jian Jiang ◽  
...  

To explore the role of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in gastric mucosal injury, 3 models of gastric mucosal injury induced by ethanol, indomethacin, or cold stress were used in rats. The cultured human gastric mucosal epithelial cell line GES-1 infected by Helicobacter pylori (Hp) was selected to mimic human gastric mucosal injury. Gastric mucosal ulcer index (UI), levels of ADMA and NO, and activity of dimethylarginine dimethylaminohydrolase (DDAH) were determined in the mucosal injury models; in Hp-infected or ADMA-treated GES-1 cells, levels of ADMA, NO, and TNF-α and activity of DDAH were measured. The results showed that UI and levels of ADMA were markedly increased and accompanied by significantly decreased DDAH activity in the mucosal injury models. Incubation of GES-1 cells with Hp increased levels of TNF-α and ADMA and decreased activity of DDAH. Administration of ADMA also increased levels of TNF-α. The results suggest that ADMA plays an important role in facilitating gastric mucosal injury, an effect which is associated with inhibiting NO synthesis and inducing inflammatory reaction.

2002 ◽  
Vol 167 (5) ◽  
pp. 2235-2240 ◽  
Author(s):  
HITOSHI MASUDA ◽  
TOSHIHIKO TSUJII ◽  
TETSUO OKUNO ◽  
KAZUNORI KIHARA ◽  
MORITAKA GOTO ◽  
...  

1999 ◽  
Vol 277 (3) ◽  
pp. G572-G576 ◽  
Author(s):  
Shigeyuki Kawachi ◽  
Adam Cockrell ◽  
F. Stephen Laroux ◽  
Laura Gray ◽  
D. Neil Granger ◽  
...  

The objectives of this study were to assess the role of the inducible isoform of nitric oxide synthase (iNOS) on vascular cell adhesion molecule 1 (VCAM-1) expression in vivo in an acute model of inflammation induced in iNOS-deficient (iNOS−/−) mice and compare these data to those obtained by pharmacological inhibition of iNOS in a CD4+ T lymphocyte-dependent model of chronic colitis. VCAM-1 expression was quantified in vivo using the dual radiolabel monoclonal antibody technique. We found that intraperitoneal injection of 10 μg/kg tumor necrosis factor-α (TNF-α) enhanced VCAM-1 expression by approximately twofold in the colon, cecum, and stomach but not small intestine in iNOS−/−mice compared with TNF-α-injected wild-type mice. Injection of wild-type mice with 25 μg/kg TNF-α further enhanced VCAM-1 expression by approximately twofold compared with wild-type mice injected with 10 μg/kg TNF-α; however, VCAM-1 expression was not further enhanced in any gastrointestinal organ system in iNOS−/− mice. In a second series of experiments, we found that continuous inhibition of iNOS using oral administration of N G-iminoethyl-l-lysine did not alter the enhanced levels of VCAM-1 expression in the colon nor did it alter the severity of colonic inflammation in SCID mice reconstituted with CD4+, CD45RBhigh T cells. We conclude that iNOS may regulate VCAM-1 expression in acute inflammation; however, this effect is modest and tissue specific and occurs only when VCAM-1 expression is submaximal. iNOS does not appear to modulate VCAM-1 expression in an immune model of chronic colitis.


1998 ◽  
Vol 64 (4) ◽  
pp. 459-466 ◽  
Author(s):  
Leslie C. McKinney ◽  
Elizabeth M. Aquilla ◽  
Deborah Coffin ◽  
David A. Wink ◽  
Yoram Vodovotz

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