Protective effects of endothelin-1 on acute pancreatitis in rats

• Published in: Digestive diseases and sciences 1995-06, Vol.40 (6), p.1207-1212
• Main Authors: KOGIRER, M, INOUE, K, HIGASHIDE, S.-I, TAKAORI, K, ECHIGO, Y, YUAN-JUN GU, SUMI, S, UCHIDA, K, IMAMURA, M
• Format: Article
• Language: English
• Subjects: Acute Disease; Amylases - blood; Amylases - drug effects; Analysis of Variance; Animals; Biological and medical sciences; Ceruletide; Disease Models, Animal; Drug Evaluation, Preclinical; Endothelin Receptor Antagonists; Endothelins - blood; Endothelins - therapeutic use; Gastroenterology. Liver. Pancreas. Abdomen; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Other diseases. Semiology; Pancreas - drug effects; Pancreas - pathology; Pancreatitis - blood; Pancreatitis - chemically induced; Pancreatitis - drug therapy; Pancreatitis - pathology; Peptides, Cyclic - therapeutic use; Rats; Rats, Wistar
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/bf02065525

Endothelin-1, a 21-residue peptide isolated from vascular endothelial cells, has a broad spectrum of actions. To clarify the involvement of endothelin-1 in acute pancreatitis, we examined the effects of endothelin-1 and its receptor antagonist BQ-123 on cerulein-induced pancreatitis in rats. Rats were infused intravenously with heparin-saline (control), endothelin-1 (100 pmol/kg/hr), cerulein (5 micrograms/kg/hr), or cerulein plus endothelin-1 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-1, 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-1 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 than BQ-123 was given with cerulein. Endothelin-1 or BQ-123 had no influence on hyperamylasemia. This study suggests that endothelin-1 has protective effects on experimental acute pancreatitis.