A1 adenosine receptor knockout mice exhibit increased renal injury following ischemia and reperfusion

H. Thomas Lee, Hua Xu, Samih H. Nasr, Jurgen Schnermann, Charles W. Emala

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Controversy exists regarding the effect of A1 adenosine receptor (AR) activation in the kidney during ischemia and reperfusion (I/R) injury. We sought to further characterize the role of A1 ARs in modulating renal function after I/R renal injury using both pharmacological and gene deletion approaches in mice. A1 AR knockout mice (A 1KO) or their wild-type littermate controls (A1WT) were subjected to 30 min of renal ischemia. Some A1WT 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 A1 AR antagonist and agonist, respectively. Plasma creatinine and renal histology were compared 24 h after renal injury. A 1KO mice exhibited significantly higher creatinines and worsened renal histology compared with A1WT controls following renal I/R injury. A1WT mice pretreated with the A1 AR antagonist or agonist demonstrated significantly worsened or improved renal function, respectively, after I/R injury. In addition, A1WT mice pretreated with DPCPX of CCPA showed significantly increased or reduced markers of renal inflammation, respectively (renal myeloperoxidase activity, renal tubular neutrophil infiltration, ICAM-1, TNF-α, and IL-1β 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.

Original languageEnglish (US)
Pages (from-to)F298-F306
JournalAmerican Journal of Physiology - Renal Physiology
Volume286
Issue number2 55-2
DOIs
StatePublished - Feb 2004

Keywords

  • Acute renal failure
  • Inflammation
  • Ischemic-repefusion injury

ASJC Scopus subject areas

  • Physiology
  • Urology

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