{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:51:21Z","timestamp":1789185081119,"version":"build-2803163510"},"reference-count":45,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p>The role of renal A<jats:sub>1<\/jats:sub>adenosine receptors (A<jats:sub>1<\/jats:sub>AR) in the pathogenesis of radiocontrast nephropathy is controversial. We aimed to further elucidate the role of A<jats:sub>1<\/jats:sub>AR in the pathogenesis of radiocontrast nephropathy and determine whether renal proximal tubule A<jats:sub>1<\/jats:sub>AR contribute to the radiocontrast nephropathy. To induce radiocontrast nephropathy, A<jats:sub>1<\/jats:sub>AR wild-type (WT) or knockout (KO) mice were injected with a nonionic radiocontrast (iohexol, 1.5\u20133 g iodine\/kg). Some A<jats:sub>1<\/jats:sub>WT mice were pretreated with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; a selective A<jats:sub>1<\/jats:sub>AR antagonist) before iohexol injection. A<jats:sub>1<\/jats:sub>AR contribute to the pathogenesis of radiocontrast nephropathy in vivo as the A<jats:sub>1<\/jats:sub>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<jats:sub>1<\/jats:sub>KO mice. DPCPX pretreatment also protected the A<jats:sub>1<\/jats:sub>WT mice against radiocontrast-induced acute renal failure. No differences in renal cortical apoptosis or inflammation were observed between A<jats:sub>1<\/jats:sub>WT and A<jats:sub>1<\/jats:sub>KO mice. To determine whether the proximal tubular A<jats:sub>1<\/jats:sub>AR mediate the direct renal cytotoxicity of radiocontrast, we treated proximal tubules in culture with iohexol with or without 2-chloro- N<jats:sup>6<\/jats:sup>-cyclopentyladenosine (a selective A<jats:sub>1<\/jats:sub>AR agonist) or DPCPX pretreatment. We also subjected cultured proximal tubule cells overexpressing A<jats:sub>1<\/jats:sub>AR or lacking A<jats:sub>1<\/jats:sub>AR to radiocontrast injury. Iohexol caused a direct dose-dependent reduction in proximal tubule cell viability as well as proliferation. Neither the A<jats:sub>1<\/jats:sub>AR agonist nor the antagonist treatment affected proximal tubule viability or proliferation. Moreover, overexpression or lack of A<jats:sub>1<\/jats:sub>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<jats:sub>1<\/jats:sub>AR; however, renal proximal tubule A<jats:sub>1<\/jats:sub>AR do not contribute to the direct tubular toxicity of radiocontrast.<\/jats:p>","DOI":"10.1152\/ajprenal.00347.2005","type":"journal-article","created":{"date-parts":[[2006,1,18]],"date-time":"2006-01-18T03:14:09Z","timestamp":1137554049000},"page":"F1367-F1375","source":"Crossref","is-referenced-by-count":66,"title":["A<sub>1<\/sub>adenosine receptor knockout mice are protected against acute radiocontrast nephropathy in vivo"],"prefix":"10.1152","volume":"290","author":[{"given":"H. 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