%0 Journal Article
%T The Reno-Vascular A2B Adenosine Receptor Protects the Kidney from Ischemia
%A Almut Grenz
%A Hartmut Osswald
%A Tobias Eckle
%A Dan Yang
%A Hua Zhang
%A Zung Vu Tran
%A Karin Klingel
%A Katya Ravid
%A Holger K Eltzschig
%J PLOS Medicine
%D 2008
%I Public Library of Science (PLoS)
%R 10.1371/journal.pmed.0050137
%X 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¨C6583 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.
%U http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050137