| First Author | Grenz A | Year | 2008 |
| Journal | PLoS Med | Volume | 5 |
| Issue | 6 | Pages | e137 |
| PubMed ID | 18578565 | Mgi Jnum | J:207364 |
| Mgi Id | MGI:5556047 | Doi | 10.1371/journal.pmed.0050137 |
| Citation | Grenz A, et al. (2008) The reno-vascular A2B adenosine receptor protects the kidney from ischemia. PLoS Med 5(6):e137 |
| abstractText | 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. |
