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

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

Author information

1
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.

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).

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.

PMID:
18578565
PMCID:
PMC2504049
DOI:
10.1371/journal.pmed.0050137
[Indexed for MEDLINE]
Free PMC Article

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