Alterations in pancreatic microcirculation and expression of endothelin-1 in a model of chronic pancreatitis.
Chronic pancreatitis (CP) is characterized by the presence of an inflammatory infiltrate with progressive destruction of acinar cells and fibrosis. The finding that endothelin-1 (ET-1), an endothelium-derived peptide having vasoconstrictive and mitogenic properties, reduces pancreatic blood flow (PBF) in normal rats suggested that the peptide may be associated with the reduced PBF seen in animal models of CP and with the morphological abnormalities of the disease. This study investigates changes in blood flow to the pancreas and other abdominal organs in a rat model of CP and compares ET-1 production in the pancreata of these rats and normal controls. CP was induced in male Wistar rats by the injection of oleic acid into the common bile/pancreatic duct. The radiolabeled microsphere technique was employed to measure blood flow to the pancreas, duodenum, liver, spleen, and kidneys. Immunohistochemistry was used to investigate the cellular production of ET-1. After 3 weeks, significant decreases were noted in body weight, pancreatic weight, and pancreatic DNA, amylase, and protein content in the animals with CP. PBF was reduced by 64% and duodenal blood flow by 80% relative to those in control animals. Hepatic and splenic blood flows were increased by 91 and 88%, respectively, compared to those in controls. A 50% decrease in renal blood flows were increased by 91 and 88%, respectively, compared to those in controls. A 50% decrease in renal blood flow was also seen in the experimental group after 3 weeks. Pancreata from animals with CP stained diffusely for ET-1 in the cytoplasm of vascular endothelial, acinar, and ductal cells. In the control pancreata, focal staining for ET-1 was observed only in acinar cells. This difference was significant in endothelial and ductal cells. There was weak staining of islet cells in both groups. The results suggest that elevation in local production of ET-1 may be associated with the morphological and hemodynamic changes of CP.
Kakugawa
Y
Y
Department of Surgery, Montreal General Hospital, Canada.
Paraskevas
S
S
Metrakos
P
P
Giaid
A
A
Qi
S J
SJ
Duguid
W P
WP
Rosenberg
L
L
D000818:Animals; D001783:Blood Flow Velocity; D002908:Chronic Disease; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D008863:Microspheres; D010179:Pancreas / Q000098:blood supply* / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow
D019332:Endothelin-1