Document Detail


Differential effects of ET-1, ET-2, and ET-3 on pancreatic microcirculation, tissue integrity, and inflammation.
MedLine Citation:
PMID:  11414314     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The differential effects of endothelin-1, -2, and -3 (ET-1, ET-2, and ET-3) on pancreatic microcirculation, pancreatic tissue integrity, and an initial inflammatory response, which are three distinct characteristics of acute necrotizing pancreatitis, were investigated in a dose-dependent manner in rats using in vivo microscopy. Red blood cell (RBC) velocity and functional capillary density (FCD) were estimated after topical superfusion of the pancreas with ET-1, ET-2, and ET-3 (100, 10, 1 pmol), revealing that ET-1 (100, 10, 1 pmol) or high ET-2 (100 pmol) and ET-3 (100 pmol) cause a dose-related deterioration of exocrine nutritive pancreatic blood flow. Analysis of pancreatic exocrine tissue damage employing the Spormann score displayed that the ET-mediated microcirculatory impairment was paralleled by dose-dependent tissue damage, which was significant compared to the control group (topical superfusion with 1 ml, saline solution 0.9%). Estimation of pancreatic postcapillary leukocyte accumulation by histomorphologically counting choracetate esterase (CAE) stained leukocytes in 50 high-power fields per animal demonstrated a significant increase in postcapillary accumulation of white blood cells, after topical administration of ET-1, ET-2, and ET-3 compared to controls. In contrast to ET-caused effects on microcirculation and tissue impairment, quantitative analysis of postcapillary leukocyte accumulation revealed the most pronounced effect after ET-2 administration but not after ET-1 administration. This demonstrates that ET-1, ET-2, and ET-3 are all able to mediate microcirculatory impairment, tissue damage, and inflammation. However, ET-3-induced damaging effects are less pronounced, while ET-1 most severely alters microcirculation and ET-2 preferentially induces leukocyte-dependent inflammation.
Authors:
T Plusczyk; B Bersal; M D Menger; G Feifel
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Digestive diseases and sciences     Volume:  46     ISSN:  0163-2116     ISO Abbreviation:  Dig. Dis. Sci.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-20     Completed Date:  2001-07-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902782     Medline TA:  Dig Dis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1343-51     Citation Subset:  AIM; IM    
Affiliation:
Department of General Surgery, University of Saarland, Homburg/Saar, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dose-Response Relationship, Drug
Endothelin-1 / pharmacology,  physiology*
Endothelin-2 / pharmacology,  physiology*
Endothelin-3 / pharmacology,  physiology*
Male
Microcirculation / drug effects
Pancreas / blood supply*,  drug effects,  immunology,  pathology
Pancreatitis, Acute Necrotizing / etiology,  immunology
Rats
Rats, Inbred Lew
Chemical
Reg. No./Substance:
0/Endothelin-1; 0/Endothelin-2; 0/Endothelin-3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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