Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 286, Issue 2, Pages F298-F306Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00185.2003
Keywords
acute renal failure; inflammation; ischemic-repefusion injury
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Funding
- NIDDK NIH HHS [R01 DK-58547] Funding Source: Medline
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Controversy exists regarding the effect of A(1) adenosine receptor (AR) activation in the kidney during ischemia and reperfusion (I/R) injury. We sought to further characterize the role of A(1) ARs in modulating renal function after I/R renal injury using both pharmacological and gene deletion approaches in mice. A(1) AR knockout mice (A(1)KO) or their wild-type littermate controls (A(1)WT) were subjected to 30 min of renal ischemia. Some A(1)WT mice were subjected to 30 min of renal ischemia with or without pretreatment with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) or 2-chrolo-cyclopentyladenosine (CCPA), selective A(1) AR antagonist and agonist, respectively. Plasma creatinine and renal histology were compared 24 h after renal injury. A(1)KO mice exhibited significantly higher creatinines and worsened renal histology compared with A(1)WT controls following renal I/R injury. A(1)WT mice pretreated with the A(1) AR antagonist or agonist demonstrated significantly worsened or improved renal function, respectively, after I/R injury. In addition, A(1)WT mice pretreated with DPCPX or CCPA showed significantly increased or reduced markers of renal inflammation, respectively (renal myeloperoxidase activity, renal tubular neutrophil infiltration, ICAM-1, TNF-alpha, and IL-1beta mRNA expression), while demonstrating no differences in indicators of apoptosis. In conclusion, we demonstrate that endogenous or exogenous preischemic activation of A(1) ARs protects against renal I/R injury in vivo via mechanisms leading to decreased necrosis and inflammation.
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