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 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.
Kogire
M
M
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Inoue
K
K
Higashide
S
S
Takaori
K
K
Echigo
Y
Y
Gu
Y J
YJ
Sumi
S
S
Uchida
K
K
Imamura
M
M
D000208:Acute Disease; D000681:Amylases / Q000097:blood / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D002108:Ceruletide; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010456:Peptides, Cyclic / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D002108:Ceruletide; D000681:Amylases; C072247:cyclo(Trp-Asp-Pro-Val-Leu)