The effect of endothelin-1, endothelin-2 and endothelin-3 in early cerulein-induced acute pancreatitis in rats.
OBJECTIVE
To assess the effect of endothelins: ET-1, ET-2 and ET-3 on trypsinogen activation, lipase activity and histological changes in the pancreas in early (4 hrs) cerulein acute pancreatitis (AP) in rats.


METHODS
In 45 Wistar rats with cerulein induced AP (2 x 40 microg/kg i.p. at 1 hour interval, the effect of endothelins at the dose 2 x 0.5 or 2 x 1.0 nmol/kg i.p. was assessed vs untreated AP; 6 healthy rats were control (C). Free active trypsin (FAT), total potential trypsin after activation with enterokinase (TPT), lipase in 12000 xg supernatants of pancreatic homogenates and the plasma alpha-amylase were assayed. The %FAT/TPT was an index of trypsinogen activation.


RESULTS
%FAT/TPT increased from 3.0 +/- 0.6 in C to 16.2 +/- 3.1 in AP (p < 0.01). ET-1 decreased this index to 4.8 +/- 1.1 after higher dose (p < 0.01); the effect of lower dose was insignificant. Attenuating effect of ET-2 was significant: 7.3 +/- 1.7 after higher dose (p < 0.05) and 6.1 +/- 0.9 after lower dose (p < 0.01). ET-3 diminished this index to 4.5 +/- 1.5 (p < 0.01) and to 6.3 +/- 2.2 (p < 0.05) respectively. Lipase activity in supernatant increased from 4.1 +/- 0.6 in C to 6.3 +/- 0.7 U/mg protein in untreated AP (p < 0.05) and plasma alpha-amylase from 7.0 +/- 0.6 in C to 25.9 +/- 4.3 U/ml in AP (p < 0.001), without essential changes in treated groups vs untreated AP. Higher doses of endothelins decreased inflammatory cell infiltration score in AP.


CONCLUSIONS
The exogenous endothelins, especially ET-2 and ET-3 and to lesser extent ET-1 exerted some protective effect in early, edematous acute pancreatitis by the attenuation of trypsinogen activation and inflammatory cell infiltration in the pancreas.
Długosz
J W
JW
Department of Gastroenterology and Internal Medicine, Medical University of Białystok, Poland. ariosto@amb.edu.pl
Nowak
K
K
Andrzejewska
A
A
Wróblewski
E
E
Dabrowski
A
A
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide / Q000009:adverse effects; D019332:Endothelin-1 / Q000494:pharmacology; D019333:Endothelin-2 / Q000494:pharmacology; D019334:Endothelin-3 / Q000494:pharmacology; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D008049:Lipase / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014362:Trypsinogen / Q000187:drug effects / Q000378:metabolism*; D000516:alpha-Amylases / Q000187:drug effects / Q000378:metabolism*
D019332:Endothelin-1; D019333:Endothelin-2; D019334:Endothelin-3; D016232:Endothelins; D002108:Ceruletide; D014362:Trypsinogen; D008049:Lipase; D000516:alpha-Amylases