Endothelin 1 induces leukocyte adhesion in submucosal venules of the rat small intestine.
OBJECTIVE
The release of endothelin 1 (ET-1) and the activation of leukocytes are involved in the pathophysiology of gastrointestinal ischemia/reperfusion injuries. The aim of this study was to define the in vivo relation between ET-1 and endothelial cell-leukocyte interactions.


METHODS
Anesthetized rats were studied to characterize the microvascular effects of increasing doses of local and systemic infusions of ET-1 in all layers of an ileal segment. Leukocyte-endothelial interactions were monitored with intravital fluorescence videomicroscopy. The ETA receptor-selective antagonist BQ 610, the novel ETA-receptor antagonist ETR-PI/fl peptide, and the ETB-receptor antagonist IRL 1038 were used to investigate the roles of receptor subtypes.


RESULTS
The functional capillary density of the mucosa was significantly decreased by 3 nmol/kg intravenous ET-1. After 30 minutes the rolling fraction of leukocytes reached 90% in the postcapillary venules, and the number of adherent leukocytes was significantly increased after 90 minutes. ETR-PI/fl peptide inhibited leukocyte rolling by 88%, BQ 610 by 73%, and IRL 1038 by 30%. Both ETA-receptor antagonists prevented ET-1-induced firm adhesion. The ETA-receptor antagonists but not IRL 1038 inhibited the ET-1-induced lymphatic muscle and mucosal capillary perfusion failure.


CONCLUSIONS
ET-1 induces leukocyte rolling and adherence through a predominantly ETA receptor-mediated mechanism in the submucosal venules of the intestinal microcirculation.
Boros
M
M
Ludwig-Maximilians University, Institute for Surgical Research, Klinikum Grosshadern, Munich, Germany.
Massberg
S
S
Baranyi
L
L
Okada
H
H
Messmer
K
K
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology*; D007421:Intestine, Small / Q000098:blood supply*; D007962:Leukocytes / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014699:Venules / Q000378:metabolism / Q000473:pathology*
D019332:Endothelin-1