A 1 adenosine receptor knockout mice are protected against acute radiocontrast nephropathy in vivo

• Published in: American journal of physiology. Renal physiology 2006-06, Vol.290 (6), p.F1367-F1375
• Main Authors: Lee, H. Thomas, Jan, Michael, Bae, Soo Chan, Joo, Jin Deok, Goubaeva, Farida R., Yang, Jay, Kim, Mihwa
• Format: Article
• Language: English
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00347.2005

The role of renal A 1 adenosine receptors (A 1 AR) in the pathogenesis of radiocontrast nephropathy is controversial. We aimed to further elucidate the role of A 1 AR in the pathogenesis of radiocontrast nephropathy and determine whether renal proximal tubule A 1 AR contribute to the radiocontrast nephropathy. To induce radiocontrast nephropathy, A 1 AR wild-type (WT) or knockout (KO) mice were injected with a nonionic radiocontrast (iohexol, 1.5–3 g iodine/kg). Some A 1 WT mice were pretreated with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; a selective A 1 AR antagonist) before iohexol injection. A 1 AR contribute to the pathogenesis of radiocontrast nephropathy in vivo as the A 1 WT mice developed significantly worse acute renal failure, more renal cortex vacuolization, and had lower survival 24 h after iohexol treatment compared with the A 1 KO mice. DPCPX pretreatment also protected the A 1 WT mice against radiocontrast-induced acute renal failure. No differences in renal cortical apoptosis or inflammation were observed between A 1 WT and A 1 KO mice. To determine whether the proximal tubular A 1 AR mediate the direct renal cytotoxicity of radiocontrast, we treated proximal tubules in culture with iohexol with or without 2-chloro- N 6 -cyclopentyladenosine (a selective A 1 AR agonist) or DPCPX pretreatment. We also subjected cultured proximal tubule cells overexpressing A 1 AR or lacking A 1 AR to radiocontrast injury. Iohexol caused a direct dose-dependent reduction in proximal tubule cell viability as well as proliferation. Neither the A 1 AR agonist nor the antagonist treatment affected proximal tubule viability or proliferation. Moreover, overexpression or lack of A 1 AR failed to impact the iohexol toxicity on proximal tubule cells. Therefore, we conclude that radiocontrast causes acute renal failure via mechanisms dependent on A 1 AR; however, renal proximal tubule A 1 AR do not contribute to the direct tubular toxicity of radiocontrast.