Endothelin receptor blockers reduce I/R-induced intestinal mucosal injury: role of blood flow.
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.
Oktar
Berna K
BK
Department of Physiology, Marmara University School of Medicine, 81326 Haydarpaşa, Istanbul, Turkey.
Gülpinar
M Ali
MA
Bozkurt
Ayhan
A
Ghandour
Salah
S
Cetinel
Sule
S
Moini
Hadi
H
Yeğen
Berrak C
BC
Bilsel
Serpil
S
Granger
D Neil
DN
Kurtel
Hizir
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002463:Cell Membrane Permeability / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D016232:Endothelins / Q000502:physiology; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000503:physiopathology; D009504:Neutrophils / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D018799:Intercellular Adhesion Molecule-1; C083116:BQ 485; C086539:BQ 788; D009195:Peroxidase; D013482:Superoxide Dismutase