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This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/F1847    most recent 00336.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Joo, J. D. Articles by Lee, H. T. Search for Related Content PubMed PubMed Citation Articles by Joo, J. D. Articles by Lee, H. T.

Acute and delayed renal protection against renal ischemia and reperfusion injury with A₁ adenosine receptors

Department of ¹Anesthesiology and ²Pathology, College of Physicians and Surgeons of Columbia University, New York, New York; and ³Department of Anesthesiology, Saint Vincent's Hospital, The Catholic University of Korea, Paldal-gu, Suwon, Gyounggi-Do, South Korea

Submitted 18 July 2007 ; accepted in final form 9 October 2007

We showed previously that activation of A₁ adenosine receptors (AR) protects against renal ischemia-reperfusion (IR) injury in rats and mice. In the heart, transient A₁AR activation produces biphasic protective effects: acute protection wanes after several hours but protective effects return 24–72 h later (second window of protection). In this study, we determined whether A₁AR activation produces delayed renal protection and elucidated the mechanisms of acute and delayed renal protection. A₁AR wild-type mice were subjected to 30-min renal ischemia and 24 h of reperfusion to produce acute renal failure. Pretreatment with a selective A₁AR agonist 2-chloro-N⁶-cyclopentyladenosine (CCPA; 0.1 mg/kg bolus ip) either 15 min or 24 h before renal ischemia protected against renal IR injury and reduced renal corticomedullary necrosis, apoptosis, and inflammation. Transient A₁AR activation led to phosphorylation of extracellular signal-regulated protein kinase mitogen-activated protein kinase (ERK MAPK), Akt, and heat shock protein 27 (HSP27). Moreover, induction of HSP27 and Akt occurred with CCPA treatment. Inhibition of PKC with chelerythrine prevented acute but not delayed renal protection with A₁AR activation. Moreover, deletion of PI3K or inhibition of Akt, but not inhibition of ERK, prevented delayed and acute renal protection with A₁AR activation. Inhibition of G_i/o with pertussis toxin obliterated both acute and delayed A₁AR-mediated renal protection. In contrast to renal protection with delayed ischemic preconditioning, nitric oxide synthase activity was not induced with delayed A₁AR-mediated renal protection. Therefore, transient activation of renal A₁AR led to acute as well as delayed protective effects against renal IR injury via distinct signaling pathways.

acute renal failure; extracellular signal-regulated protein kinase/mitogen-activated protein kinase; heat shock protein 27; mice; protein kinase B/Akt