Endothelin receptor blockers reduce I/R-induced intestinal mucosal injury: role of blood flow


Oktar B., Gulpinar M. A. , Bozkurt A., Ghandour S., Cetinel S., Moini H., ...More

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, vol.282, no.4, 2002 (Journal Indexed in SCI) identifier

  • Publication Type: Article / Article
  • Volume: 282 Issue: 4
  • Publication Date: 2002
  • Title of Journal : AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
  • Keywords: mucosal permeability, mucosal injury, BQ-485, BQ-788, superoxide dismutase, ISCHEMIA-REPERFUSION, ENDOGENOUS ENDOTHELIN-1, PULMONARY-CIRCULATION, HEMORRHAGIC-SHOCK, ET(B) RECEPTORS, MECHANISMS, CLEARANCE, ARTERIAL, PATHOPHYSIOLOGY, GRANULOCYTES

Abstract

The aim of the present study was to assess the role of endothelin (ET) in ischemia-reperfusion (I/R)-induced mucosal injury. Mucosal permeability (Cr-51-EDTA clearance) and tissue myeloperoxidase (MPO) activity were significantly increased after 30 min of ischemia followed by 30 min of reperfusion. The I/R-induced increases in mucosal permeability and polymorphonuclear leukocyte (PMN) infiltration were significantly attenuated by pretreatments with ETA (BQ-485) and/or ETB (BQ-788) receptor antagonists. Monoclonal antibody (MAb) directed against intercellular adhesion molecule-1 (ICAM-1; MAb 1A29) and superoxide dismutase (SOD) pretreatments significantly attenuated the increased mucosal permeability and PMN infiltration in a similar manner as with ET receptor antagonists. Superior mesenteric artery blood flow was significantly reduced during the reperfusion period. Both ET receptor antagonists caused a significant rise in blood flow compared with an untreated I/R group. In conclusion, our data suggest that ETA and/or ETB receptors, ICAM-1, and superoxide play an important role in I/R-induced mucosal dysfunction and PMN infiltration. Furthermore, ET is involved in the pathogenesis of postreperfusion-induced damage and beneficial effects of ET receptor antagonism are related to an improvement of disturbed blood flow during the reperfusion period.