Selective A2A adenosine receptor activation reduces ischemia-reperfusion injury in rat kidney

Am J Physiol. 1999 Sep;277(3):F404-12. doi: 10.1152/ajprenal.1999.277.3.F404.


A2A adenosine receptors (A2A-ARs) are known modulators of renal hemodynamics and potent inhibitors of inflammation. We sought to determine whether selective activation of A2A-ARs protects kidneys from ischemia-reperfusion injury. The ester derivative of DWH-146 (DWH-146e), a selective A2A agonist, was found to be more potent and selective for A2A-ARs than the prototype compound CGS-21680. Osmotic minipumps were implanted subcutaneously to infuse into rats either vehicle or DWH-146e (0.004 microg. kg(-1). min(-1)), during and after ischemia-reperfusion injury. Following 24 and 48 h of reperfusion, the rise in serum creatinine and blood urea nitrogen for vehicle-treated rats was substantially elevated compared with DWH-146e-treated rats. Histological examination revealed widespread tubular epithelial necrosis and vascular congestion in the outer medulla of vehicle-treated compared with DWH-146e-treated animals. ZM-241385, a selective A(2A) antagonist, blocked the protective effect of DWH-146e. Delaying administration of DWH-146e until the initiation of reperfusion also decreased serum creatinine. We conclude that 1) selective A2A-AR activation by DWH-146e reduces ischemia-reperfusion injury in rat kidneys, 2) the effect of DWH-146e is A2A receptor mediated, and 3) the protective effects are mediated by preventing injury during the reperfusion period.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Kidney / blood supply
  • Kidney / pathology
  • Kidney / physiopathology*
  • Male
  • Necrosis
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P1 / physiology*
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology*
  • Triazines / pharmacology
  • Triazoles / pharmacology


  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1
  • Triazines
  • Triazoles
  • ZM 241385