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Updated: Jul 4, 2026
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
The reno-vascular A2B adenosine receptor protects the kidney from ischemia
Almut Grenz1, Hartmut Osswald, Tobias Eckle
1Department 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.
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.
Insights
Researchers discovered that activating adenosine A2B receptors (A2BAR) protects kidneys from ischemic injury. This finding highlights A2BAR as a potential therapeutic target for preventing acute renal failure and improving patient outcomes.
Area of Science:
- Nephrology
- Cardiovascular Research
- Molecular Pharmacology
Background:
- Acute kidney injury from ischemia is a major clinical concern.
- Effective strategies to enhance renal ischemia resistance are critically needed.
- Ischemic preconditioning (IP) offers a protective pathway against renal ischemia.
Purpose of the Study:
- To identify novel pathways involved in renal protection during ischemic preconditioning (IP).
- To investigate the role of adenosine receptors (ARs) in mediating renal protection from ischemia.
- To determine the therapeutic potential of targeting specific adenosine receptors for renal ischemia.
Main Methods:
- Utilized a novel mouse model for reproducible renal ischemia and IP.
- Employed gene-targeted mice lacking individual adenosine receptors (A1, A2A, A3, A2B).
- Assessed renal function, inflammation, and nitric oxide production post-ischemia.
- Administered A2BAR antagonists and agonists to evaluate their effects on renal ischemia.
- Investigated A2BAR expression and localization using reporter models and bone-marrow chimeras.
Main Results:
- IP conferred renal protection in mice lacking A1, A2A, or A3 ARs.
- Renal protection by IP was abolished in mice lacking A2B ARs (A2BAR-/-).
- A2BAR antagonism blocked IP-mediated protection, while A2BAR agonism improved outcomes after ischemia.
- A2BARs are exclusively expressed in the renal vasculature, and protection is conferred by renal A2BARs.
Conclusions:
- Adenosine A2B receptor (A2BAR) is identified as a key mediator of renal protection from ischemia.
- Targeting A2BAR represents a novel therapeutic strategy for preventing renal ischemia.
- A2BAR activation offers potent protection against ischemic acute kidney injury.
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