Journal of Gastroenterology

, Volume 30, Issue 5, pp 636–642 | Cite as

Nitric oxide modulates pancreatic edema formation in rat caerulein-induced pancreatitis

  • Takashi Abe
  • Tooru Shimosegawa
  • Akihiko Satoh
  • Reishi Abe
  • Yoshifumi Kikuchi
  • Masaru Koizumi
  • Takayoshi Toyota
Liver, Pancreas, and Biliary Tract


This study was designed to investigate the role of nitric oxide (NO) in the formation of pancreatic edema in caerulein-induced pancreatitis in rats. Pancreatitis was produced by two intraperitoneal injections of caerulein, and plasma amylase concentration, pancreatic edema index (pancreatic wet weight/body weight), and Evans blue extravasation (as a measure of vascular permeability) were evaluated 5h after the first injection. Four doses (1, 2.5, 5, and 10 mg/kg) of NG-nitro-L-arginine (l-NNA), an NO synthase inhibitor, were subcutaneously administered at −0.5, 0.5, 1.5, 2.5, and 3.5h after the first injection of caerulein.l-NNA significantly lowered the edema index, the wet/dry weight ratio of the pancreas, and Evans blue extravasation in the rats with pancreatitis. The maximal effect was obtained byl-NNA at a dose of 2.5 mg/kg; this inhibited the increase in pancreatic edema formation from the control value by 60%–70%. Intraperitoneal injections (20 mg/kg, five times) ofl-arginine, a substrate for NO production, partly reversed thel-NNA-induced inhibition of pancreatic edema formation, butd-arginine, an enantiomer ofl-arginine, did not show any effect. Plasma amylase concentrations were not significantly affected by any dose of L-NNA, nor were they affected byl- ord-arginine. These findings strongly suggest that endogenous NO plays an important role in the formation of pancreatic edema in caerulein-induced pancreatitis in rats, probably by increasing vascular permeability and protein extravasation.

Key Words

nitric oxide (NO) NO synthase inhibitor caerulein-induced pancreatitis pancreatic edema vascular permeability 


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Takashi Abe
    • 1
  • Tooru Shimosegawa
    • 1
  • Akihiko Satoh
    • 1
  • Reishi Abe
    • 1
  • Yoshifumi Kikuchi
    • 1
  • Masaru Koizumi
    • 1
  • Takayoshi Toyota
    • 1
  1. 1.The Third Department of Internal MedicineTohoku University School of MedicineSendai, MiyagiJapan

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