Influence of capsaicin-sensitive afferent neurons and nitric oxide (NO) on cerulein-induced pancreatitis in rats.
CONCLUSIONS
Stimulation of afferent neurons by capsaicin exerts protective activity against cerulein-induced pancreatitis. This action is dependent on endogenous release of nitric oxide (NO). Deactivation of afferent neurons by high doses of capsaicin contributes to the severity of pancreatitis. This action involves mainly decreased pancreatic blood flow (PBF). Afferent nerves and NO cooperate in the maintenance of the integrity of pancreatic tissue.


BACKGROUND
Stimulation of capsaicin-sensitive afferent fibers protects gastric mucosa against damage and causes changes in mucosal blood flow. The aim of the present study was to determine the role of stimulation or ablation of capsaicin-sensitive neurons and NO in the course of cerulein-induced pancreatitis in the rat.


METHODS
Low and high doses of capsaicin were administered to animals with pancreatitis and to those without pancreatitis. The effect of several parameters was assessed. NO activity was blocked by NG-nitro-L-arginine.


RESULTS
We found that a low dose of capsaicin administered intragastrically caused an increase in PBF. A neurotoxic dose of capsaicin caused a decrease in PBF, RNA content, and DNA synthesis. Pancreatitis led to a significant decrease in PBF and DNA synthesis, but an increase in pancreatic weight, protein content, plasma amylase concentration, and neutrophil adherence. Stimulatory doses of capsaicin attenuated the pancreatic tissue damage of pancreatitis, and alteration of PBF, DNA synthesis, and neutrophil adherence. Capsaicin-induced ablation of afferent neurons caused an increase in all indicators of pancreatic damage. Blocking NO enhanced pancreatic damage, and this was reversed by addition of L-arginine.
Dembinski
A
A
Institute of Physiology, Collegium Medicum, Jagiellonian University, Krakow, Poland.
Warzecha
Z
Z
Konturek
P J
PJ
Ceranowicz
P
P
Konturek
S J
SJ
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D002108:Ceruletide; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D009569:Nitric Oxide / Q000009:adverse effects / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010179:Pancreas / Q000098:blood supply; D010195:Pancreatitis / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D002108:Ceruletide; D001120:Arginine; D002211:Capsaicin