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 ETA receptor antagonist).


METHODS
The rat model was made by 5-hour restraint water-immersion stress and two intraperitoneal injections of cerulein (40 micrograms/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.
Liu
X
X
Department of Gastroenterology, Chinese Academy of Medical Science, Peking Union Medical College Hospital, Beijing 100730, China.
Nakano
I
I
Ito
T
T
Kimura
T
T
Nawata
H
H
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D002108:Ceruletide; C072247:cyclo(Trp-Asp-Pro-Val-Leu)