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-1 in acute pancreatitis, we examined the effects of endothelin-1 and its receptor antagonist BQ-123 on cerulein-induced pancreatitis in rats. Rats we...

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Bibliographic Details
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
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Summary: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.
ISSN:0163-2116
1573-2568
DOI:10.1007/bf02065525