title: The reno-vascular A2B adenosine receptor protects the kidney from ischemia.
abstract: 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).
  
  
  RESULTS
  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.
authors.affiliation: Department of Pharmacology and Toxicology, Tübingen University Hospital, Tübingen, Germany.Mucosal Inflammation Program, Department of Anesthesiology and Perioperative Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA.
authors.forename: Almut
authors.initials: A
authors.lastname: Grenz
authors.forename: Hartmut
authors.initials: H
authors.lastname: Osswald
authors.forename: Tobias
authors.initials: T
authors.lastname: Eckle
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Zung Vu
authors.initials: ZV
authors.lastname: Tran
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.forename: Katya
authors.initials: K
authors.lastname: Ravid
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
mesh_terms: D000241:Adenosine / Q000378:metabolism; D058917:Adenosine A2 Receptor Antagonists; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics*; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000235:genetics; D007511:Ischemia / Q000235:genetics*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D014970:Xanthines / Q000494:pharmacology
chemical_list: C518874:1-propyl-8-(4-sulfophenyl)xanthine; D058917:Adenosine A2 Receptor Antagonists; D000631:Aminopyridines; C518875:BAY 60-6583; D043704:Receptor, Adenosine A2B; D014970:Xanthines; D009569:Nitric Oxide; D000241:Adenosine