The reno-vascular A2B adenosine receptor protects the kidney from ischemia |
| |
Authors: | Grenz Almut Osswald Hartmut Eckle Tobias Yang Dan Zhang Hua Tran Zung Vu Klingel Karin Ravid Katya Eltzschig Holger K |
| |
Institution: | Department of Pharmacology and Toxicology, Tübingen University Hospital, Tübingen, Germany.Mucosal Inflammation Program, Department of Anesthesiology and Perioperative Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA. |
| |
Abstract: | BackgroundAcute 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 FindingsFor 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.ConclusionsThese results identify the A2BAR as a novel therapeutic target for providing potent protection from renal ischemia. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|