The Reno-Vascular A2B Adenosine Receptor Protects the Kidney from Ischemia

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dc.contributor.author Grenz, Almut en_US
dc.contributor.author Osswald, Hartmut en_US
dc.contributor.author Eckle, Tobias en_US
dc.contributor.author Yang, Dan en_US
dc.contributor.author Zhang, Hua en_US
dc.contributor.author Tran, Zung Vu en_US
dc.contributor.author Klingel, Karin en_US
dc.contributor.author Ravid, Katya en_US
dc.contributor.author Eltzschig, Holger K en_US
dc.date.accessioned 2012-01-12T17:43:50Z
dc.date.available 2012-01-12T17:43:50Z
dc.date.issued 2008-6-24 en_US
dc.identifier.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) en_US
dc.identifier.issn 1549-1676 en_US
dc.identifier.uri http://hdl.handle.net/2144/3431
dc.description.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. en_US
dc.description.sponsorship Deutsche Forschungsgemeinschaft Research Fellowship (GR2121/1–1); Fortune grant (1416-0-0); Interdisciplinary Centre for Clinical Research Verbundprojekt (1597-0-0); University of Tu¨ bingen; German Research Foundation (EL274/2–2); Foundation for Anesthesia Education and Research; IZKF Nachwuchsgruppe (1605-0-0) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.title The Reno-Vascular A2B Adenosine Receptor Protects the Kidney from Ischemia en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pmed.0050137 en_US
dc.identifier.pubmedid 18578565 en_US
dc.identifier.pmcid 2504049 en_US

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