Differential Effects of ET-1, ET-2, and ET-3 on Pancreatic Microcirculation, Tissue Integrity, and Inflammation

Authors: Plusczyk T.¹; Bersal B.¹; Menger M.D.²; Feifel G.¹

Source: Digestive Diseases and Sciences, Volume 46, Number 6, June 2001 , pp. 1343-1351(9)

Publisher: Springer

Abstract:

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.

Keywords: in vivo microscopy; pancreas; pancreatic microcirculation; endothelin-1; endothelin-2; endothelin-3; inflammation

Language: English

Document Type: Regular paper

Affiliations: 1: Department of General Surgery, University of Saarland, 66421 Homburg/Saar, Germany. 2: Institute for Clinical & Experimental Surgery, University of Saarland, 66421 Homburg/Saar, Germany.

Publication date: 2001-06-01

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• In this Subject: Gastroenterology
• By this author: Plusczyk T. ;  Bersal B. ;  Menger M.D. ;  Feifel G.

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