The Reno-Vascular A2B Adenosine Receptor Protects the Kidney from Ischemia
Tran, Zung Vu
Eltzschig, Holger K.
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Citation (published version)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)
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.