A(2A) adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion.
We sought to determine the mechanisms responsible for the reduced renal tissue injury by agonists of A(2A) adenosine receptors (A(2A)-ARs) in models of ischemia-reperfusion (I/R) injury. DWH-146e, a selective A(2A)-AR agonist, was administered subcutaneously to Sprague-Dawley rats and C57BL/6 mice via osmotic minipumps, and animals were subjected to I/R. I/R led to an increase in plasma creatinine and kidney neutrophil infiltration. Infusion of DWH-146e at 10 ng. kg(-1). min(-1) produced a 70% reduction in plasma creatinine as well as a decrease in neutrophil density in outer medulla and cortex and myeloperoxidase activity in the reperfused kidney. Myeloperoxidase activity in kidney correlated with the degree of renal injury. P-selectin and intercellular adhesion molecule 1 (ICAM-1) immunoreactivity were most prominent in endothelial cells of peritubular capillaries and interlobular arteries of cortex and outer and inner medulla of vehicle-treated mice whose kidneys were subjected to I/R. DWH-146e treatment led to a pronounced decrease in P-selectin- and ICAM-1-like immunoreactivity. These data are consistent with our hypothesis that A(2A)-AR agonists limit I/R injury due to an inhibitory effect on neutrophil adhesion.
Okusa
M D
MD
Department of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. mdo7y@virginia.edu
Linden
J
J
Huang
L
L
Rieger
J M
JM
Macdonald
T L
TL
Huynh
L P
LP
D058186:Acute Kidney Injury / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002452:Cell Count; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D007279:Injections, Subcutaneous; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D019007:P-Selectin / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D019007:P-Selectin; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D018799:Intercellular Adhesion Molecule-1; D003404:Creatinine; D009195:Peroxidase