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

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2002-04, Vol.282 (4), p.G647-G655
• Main Authors: Oktar, Berna K, Gülpinar, M Ali, Bozkurt, Ayhan, Ghandour, Salah, Cetinel, Sule, Moini, Hadi, Yeğen, Berrak C, Bilsel, Serpil, Granger, D Neil, Kurtel, Hizir
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Azepines - pharmacology; Blood Flow Velocity; Blood Pressure; Cell Membrane Permeability - drug effects; Endothelin Receptor Antagonists; Endothelin-1 - blood; Endothelins - physiology; Female; Intercellular Adhesion Molecule-1 - immunology; Intercellular Adhesion Molecule-1 - physiology; Intestinal Mucosa - blood supply; Intestinal Mucosa - pathology; Intestinal Mucosa - physiopathology; Male; Mesenteric Artery, Superior - physiopathology; Neutrophils - pathology; Oligopeptides - pharmacology; Peroxidase - metabolism; Piperidines - pharmacology; Rats; Rats, Wistar; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin - physiology; Reperfusion Injury - prevention & control; Superoxide Dismutase - immunology; Superoxide Dismutase - physiology
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.2002.282.4.g647

The aim of the present study was to assess the role of endothelin (ET) in ischemia-reperfusion (I/R)-induced mucosal injury. Mucosal permeability ((51)Cr-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 ET(A) (BQ-485) and/or ET(B) (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 ET(A) and/or ET(B) 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 post-reperfusion-induced damage and beneficial effects of ET receptor antagonism are related to an improvement of disturbed blood flow during the reperfusion period.