The reno-vascular A2B adenosine receptor protects the kidney from ischemia

PLoS Med. 2008 Jun 24;5(6):e137. doi: 10.1371/journal.pmed.0050137.


Background: Acute renal failure from ischemia significantly contributes to morbidity and mortality in clinical settings, and strategies to improve renal resistance to ischemia are urgently needed. Here, we identified a novel pathway of renal protection from ischemia using ischemic preconditioning (IP).

Methods and findings: For this purpose, we utilized a recently developed model of renal ischemia and IP via a hanging weight system that allows repeated and atraumatic occlusion of the renal artery in mice, followed by measurements of specific parameters or renal functions. Studies in gene-targeted mice for each individual adenosine receptor (AR) confirmed renal protection by IP in A1(-/-), A2A(-/-), or A3AR(-/-) mice. In contrast, protection from ischemia was abolished in A2BAR(-/-) mice. This protection was associated with corresponding changes in tissue inflammation and nitric oxide production. In accordance, the A2BAR-antagonist PSB1115 blocked renal protection by IP, while treatment with the selective A2BAR-agonist BAY 60-6583 dramatically improved renal function and histology following ischemia alone. Using an A2BAR-reporter model, we found exclusive expression of A2BARs within the reno-vasculature. Studies using A2BAR bone-marrow chimera conferred kidney protection selectively to renal A2BARs.

Conclusions: These results identify the A2BAR as a novel therapeutic target for providing potent protection from renal ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Adenosine A2 Receptor Antagonists
  • Aminopyridines / pharmacology
  • Animals
  • Blood Vessels / metabolism
  • Cytoprotection / drug effects
  • Cytoprotection / genetics*
  • Extracellular Fluid / metabolism
  • Female
  • Inflammation / genetics
  • Ischemia / genetics*
  • Kidney / blood supply*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide / metabolism
  • Receptor, Adenosine A2B / genetics
  • Receptor, Adenosine A2B / metabolism
  • Receptor, Adenosine A2B / physiology*
  • Signal Transduction / genetics
  • Xanthines / pharmacology


  • 1-propyl-8-(4-sulfophenyl)xanthine
  • Adenosine A2 Receptor Antagonists
  • Aminopyridines
  • BAY 60-6583
  • Receptor, Adenosine A2B
  • Xanthines
  • Nitric Oxide
  • Adenosine