The role of nitric oxide in mouse cerulein-induced pancreatitis with and without lipopolysaccharide pretreatment.
Nitric oxide (NO) has been shown to play a significant role in inflammation. To clarify the role of NO in acute pancreatitis, we investigated the serum concentrations of NO chi (NO2- plus NO3-) and tumor necrosis factor-alpha (TNF-alpha) and the grade of pancreatitis in cerulein-induced pancreatitis in mice pretreated with lipopolysaccharide (LPS) or not. LPS pretreatment aggravated the cerulein pancreatitis in association with a transient increase in serum TNF-alpha, which was followed by a gradual elevation of serum NO chi. This elevation of serum NO chi concentration was inhibited by the NO synthase inhibitor NG-nitro-L-arginine (L-NNA). In addition, the activity of NADPH-diaphorase (NADPH-d), a marker for NO synthase, appeared in the peritoneal macrophages of LPS-pretreated mice after the induction of pancreatitis. No elevation of serum NO chi or appearance of NADPH-d activity in peritoneal cells was found in mice without LPS pretreatment. Administration of L-NNA enhanced the elevation of pancreatitis-induced serum amylase in mice untreated with LPS, while L-NNA inhibited the elevation in LPS-pretreated mice. The effects of L-NNA were reversed by the administration of L-arginine but were not affected by D-arginine. These results suggested that (a) inflammatory cells may not be fully activated to produce excessive NO in uncomplicated edematous pancreatitis, and (b) edematous pancreatitis may be aggravated by excessively produced NO if bacterial infection is complicated and inflammatory cells are activated to express inducible NO synthase.
Kikuchi
Y
Y
Third Department of Internal Medicine, Tohoku University School of Medicine, Miyagi, Japan.
Shimosegawa
T
T
Satoh
A
A
Abe
R
R
Abe
T
T
Koizumi
M
M
Toyota
T
T
D000818:Animals; D002108:Ceruletide; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000097:blood*; D010195:Pancreatitis / Q000097:blood* / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002108:Ceruletide