[A.sub.2A] adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion

Okusa, Mark D., Joel Linden, Liping Huang, Jayson M. Rieger, Timothy L. Macdonald, and Long P. Huynh. [A.sub.2A] adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion. Am J Physiol Renal Physiol 279: FS09-F818, 2000.--We sought to determine the mechanisms responsible for the reduced renal tissue injury by agonists of [A.sub.2A] adenosine receptors ([A.sub.2A]-ARs) in models of ischemia-reperfusion (I/R) injury. DWH-146e, a selective [A.sub.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 [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-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.sub.2A]-AR agonists limit I/R injury due to an inhibitory effect on neutrophil adhesion. acute renal failure; neutrophil-endothelial cell interaction; intercellualr adhesion molecule 1; P-selectin