Role of endothelin in the pathophysiology of renal ischemia-reperfusion in normal rabbits.
The present study addressed the acute effects of endothelin-1 on renal function and neutrophils accumulation in the setting of in vivo severe (60 min) acute ischemia/reperfusion. Ischemia/reperfusion decreased renal functional parameters and increased renal neutrophil accumulation and medullary congestion. All these parameters markedly improved with the intrarenal administration of anti-endothelin-1 antiserum. Comparatively, the intrarenal infusion of endothelin-1 decreased renal function and increased neutrophil accumulation. Abnormalities in renal histology were, however, less pronounced than with ischemia/ reperfusion. In experiments using rabbit isolated perfused kidneys, endothelin-1 induced the accumulation of labeled neutrophils. This accumulation was similar to that observed in kidneys obtained after 60 minutes of ischemia plus 60 minutes of reperfusion. Both endothelin and ischemia/ reperfusion effects were counteracted by an anti-endothelin antibody. In further in vitro studies, we found that endothelin-1-induced the expression of the CD18 antigens on the neutrophil surface. In subsequent experiments based on this effect of ET-1 on CD18 antigens, a blockade of both ischemia/reperfusion-induced and endothelin-1-induced neutrophil accumulation was obtained by infusion an anti-CD18 antibody. In conclusion, our experiments disclosed the critical role of endothelin-1 as a major promoter of early neutrophil accumulation after ischemia/reperfusion, which occurred through an integrin-mediated mechanism.
Espinosa
G
G
Laboratorio de Nefrología e Hipertensión, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
López Farré
A
A
Cernadas
M R
MR
Manzarbeitia
F
F
Tan
D
D
Digiuni
E
E
Mosquera
J R
JR
Montón
M
M
Millás
I
I
Hernando
L
L
Casado
S
S
Caramelo
C
C
D000818:Animals; D019332:Endothelin-1 / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D005434:Flow Cytometry; D007668:Kidney / Q000098:blood supply* / Q000166:cytology; D007674:Kidney Diseases / Q000276:immunology / Q000503:physiopathology*; D007677:Kidney Function Tests; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D009924:Organ Culture Techniques; D010477:Perfusion; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology*
D019332:Endothelin-1; D009195:Peroxidase