Is endothelin-1 an aggravating factor in the development of acute pancreatitis?

Objective We have reported previously that cerulein-induced edematous pancreatitis would transform into hemorrhagic pancreatitis by administration of endothelin-1 in rats. In the present study, we tried to protect rat model from developing into hemorrhagic pancreatitis with BQ₁₂₃(an ET_A receptor antagonist). Methods The rat model was made by 5-hour restraint water-immersion stress and two intraperitoneal injections of cerulein (40 μg/kg) at hourly interval. BQ₁₂₃(3 or 6 mg/kg) was administered intravenously 30 minutes before and 2 hours after the first cerulein injection. Results Acute hemorrhagic pancreatitis was induced in all rats treated with cerulin + stress. The score for pancreatic hemorrhage was 2.4 ± 0.2 in this group. In the rats pretreated with BQ₁₂₃, the score was reduced to 1.0 ± 0.0, pancreas wet weight and serum amylase activity were significantly reduced, and histologic alterations in the pancreas lightened, also the local pancreatic blood flow improved without affecting the systemic blood pressure. Conclusions These results suggest that endothelin-1 should play a role in aggravating the development of acute hemorrhagic pancreatitis, through its action on the pancreatic microcirculation.