Nitric oxide modulates pancreatic edema formation in rat caerulein-induced pancreatitis.
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 5 h 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 3.5 h 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 by L-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) of L-arginine, a substrate for NO production, partly reversed the L-NNA-induced inhibition of pancreatic edema formation, but D-arginine, an enantiomer of L-arginine, did not show any effect. Plasma amylase concentrations were not significantly affected by any dose of L-NNA, nor were they affected by L- or D-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.
Abe
T
T
Third Department of Internal Medicine, Tohoku University School of Medicine, Miyagi, Japan.
Shimosegawa
T
T
Satoh
A
A
Abe
R
R
Kikuchi
Y
Y
Koizumi
M
M
Toyota
T
T
D000208:Acute Disease; D000681:Amylases / Q000097:blood / Q000187:drug effects; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002199:Capillary Permeability / Q000502:physiology*; D002108:Ceruletide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000209:etiology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005070:Evans Blue; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D005070:Evans Blue; D002108:Ceruletide; D001120:Arginine; D000681:Amylases