The Reno-Vascular A2B Adenosine Receptor Protects the Kidney from Ischemia
Date
2008-6-24
Authors
Grenz, Almut
Osswald, Hartmut
Eckle, Tobias
Yang, Dan
Zhang, Hua
Tran, Zung Vu
Klingel, Karin
Ravid, Katya
Eltzschig, Holger K.
Version
OA Version
Citation
Grenz, Almut, Hartmut Osswald, Tobias Eckle, Dan Yang, Hua Zhang, Zung Vu Tran, Karin Klingel, Katya Ravid, Holger K Eltzschig. "The Reno-Vascular A2B Adenosine Receptor Protects the Kidney from Ischemia" PLoS Medicine 5(6):e137. (2008)
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. Using gene-targeted mice, Holger Eltzschig and colleagues identify the A2B adenosine receptor as a novel therapeutic target for providing protection from renal ischemia.