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This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/F1367    most recent 00347.2005v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Lee, H. T. Articles by Kim, M. Search for Related Content PubMed PubMed Citation Articles by Lee, H. T. Articles by Kim, M.

A₁ adenosine receptor knockout mice are protected against acute radiocontrast nephropathy in vivo

Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York

Submitted 25 August 2005 ; accepted in final form 14 January 2006

The role of renal A₁ adenosine receptors (A₁AR) in the pathogenesis of radiocontrast nephropathy is controversial. We aimed to further elucidate the role of A₁AR in the pathogenesis of radiocontrast nephropathy and determine whether renal proximal tubule A₁AR contribute to the radiocontrast nephropathy. To induce radiocontrast nephropathy, A₁AR wild-type (WT) or knockout (KO) mice were injected with a nonionic radiocontrast (iohexol, 1.5–3 g iodine/kg). Some A₁WT mice were pretreated with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; a selective A₁AR antagonist) before iohexol injection. A₁AR contribute to the pathogenesis of radiocontrast nephropathy in vivo as the A₁WT mice developed significantly worse acute renal failure, more renal cortex vacuolization, and had lower survival 24 h after iohexol treatment compared with the A₁KO mice. DPCPX pretreatment also protected the A₁WT mice against radiocontrast-induced acute renal failure. No differences in renal cortical apoptosis or inflammation were observed between A₁WT and A₁KO mice. To determine whether the proximal tubular A₁AR mediate the direct renal cytotoxicity of radiocontrast, we treated proximal tubules in culture with iohexol with or without 2-chloro-N⁶-cyclopentyladenosine (a selective A₁AR agonist) or DPCPX pretreatment. We also subjected cultured proximal tubule cells overexpressing A₁AR or lacking A₁AR to radiocontrast injury. Iohexol caused a direct dose-dependent reduction in proximal tubule cell viability as well as proliferation. Neither the A₁AR agonist nor the antagonist treatment affected proximal tubule viability or proliferation. Moreover, overexpression or lack of A₁AR failed to impact the iohexol toxicity on proximal tubule cells. Therefore, we conclude that radiocontrast causes acute renal failure via mechanisms dependent on A₁AR; however, renal proximal tubule A₁AR do not contribute to the direct tubular toxicity of radiocontrast.

acute renal failure; HK-2 cells; iohexol; knockout mice; LLC-PK₁ cells; vasoconstriction