PROTECTIVE EFFECTS OF ENDOTHELIN-1 ON ACUTE-PANCREATITIS IN RATS

Endothelin-1, a 21-residue peptide isolated from vascular endothelial cells, has a broad spectrum of actions. To clarify the involvement of endothelin-l in acute pancreatitis, we examined the effects of endothelin-l and its receptor antagonist BQ-123 on cerulein-induced pancreatitis in rats. Rats were infused intravenously with heparin-saline (control), endothelin-l (100 pmol/kg/hr), cerulein (5 mu g/kg/hr), or cerulein plus endothelin-l for 3.5 hr. In another experiment, cerulein or cerulein plus BQ-123 (3 mg/kg/hr) was infused. Infusion of cerulein caused hyperamylasemia and pancreatic edema. Endothelin-l, when infused with cerulein, decreased the extent of pancreatic edema with a significant increase in the pancreatic dry- to wet-weight ratio. Histological changes induced by cerulein were markedly attenuated when endothelin-l was given with cerulein. In contrast, endothelin-receptor blockade with BQ-123 further augmented pancreatic edema caused by cerulein. The extent of inflammatory cell infiltration was greater when BQ-123 was given with cerulein. Endothelin-l or BQ-123 had no influence on hyperamylasemia. This study suggests that endothelin-l has protective effects on experimental acute pancreatitis.