A(2A) adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion

We sought to determine the mechanisms responsible for the reduced renal tis sue injury by agonists of A(2A) adenosine receptors (A(2A)-ARs) in models o f ischemia-reperfusion (I/R) injury. DWH-146e, a selective A(2A)-AR agonist , was administered subcutaneously to Sprague-Dawley rats and C57BL/6 mice v ia osmotic minipumps, and animals were subjected to I/R. I/R led to an incr ease in plasma creatinine and kidney neutrophil infiltration. Infusion of D WH-146e at 10 ng . kg(-1). min(-1) produced a 70% reduction in plasma creat inine as well as a decrease in neutrophil density in outer medulla and cort ex and myeloperoxidase activity in the reperfused kidney. Myeloperoxidase a ctivity in kidney correlated with the degree of renal injury. P-selectin an d intercellular adhesion molecule 1 (ICAM-1) immunoreactivity were most pro minent in endothelial cells of peritubular capillaries and interlobular art eries of cortex and outer and inner medulla of vehicle-treated mice whose k idneys were subjected to I/R. DWH-146e treatment led to a pronounced decrea se in P-selectin- and ICAM-1-like immunoreactivity. These data are consiste nt with our hypothesis that A(2A)-AR agonists limit I/R injury due to an in hibitory effect on neutrophil adhesion.