Nitric oxide in pancreatic secretion and hormone-induced pancreatitis in rats.
The aim of the present study was to determine the role of endogenous nitric oxide (NO) in pancreatic secretion in vivo and amylase release from pancreatic acini in vitro and in caerulein-induced acute pancreatitis in rats. Blockade of NO synthase by NG-nitro-L-arginine (L-NNA) (2.5 mg/kg i.v.) significantly reduced basal pancreatic protein secretion and that induced by the infusion of CCK (0.5 micrograms/kg-h), feeding, and the diversion of pancreatic juice in rats with pancreatic fistula. This inhibitory effect was partially reversed when L-arginine (50 mg/kg-h i.v.) was added to L-NNA. L-Arginine alone (50 mg/kg i.v.) did not affect basal or caerulein-induced pancreatic secretion. L-NNA, L-arginine, or their combination added in various concentrations to the incubation medium of dispersed acini failed to affect basal or secretagogue (caerulein or urecholine) stimulated amylase release. Infusion of caerulein (5 micrograms/kg-h) for 5 h produced histological changes of acute edematous pancreatitis accompanied by a marked increase in pancreatic protein content and about 50% reduction in tissue blood flow. L-NNA alone also reduced the pancreatic blood flow and caused a significant increase in pancreatic weight and protein content. L-NNA significantly potentiated the inflammatory changes in the pancreas caused by caerulein. Addition of L-arginine enhanced the pancreatic blood flow and ameliorated the pancreatitis induced by caerulein alone or that combined with L-NNA. We conclude that NO is involved in the stimulation of pancreatic secretion in vivo and exhibits a beneficial effect on pancreatitis, probably by improving the pancreatic blood flow.
Konturek
S J
SJ
Department of Cell Pathology, Academy of Medicine, Krakow, Poland.
Szlachcic
A
A
Dembinski
A
A
Warzecha
Z
Z
Jaworek
J
J
Stachura
J
J
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002108:Ceruletide; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D010179:Pancreas / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology
D019335:Nitroarginine; D009569:Nitric Oxide; D002108:Ceruletide; D001120:Arginine; D000681:Amylases; D012844:Sincalide