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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/F1109    most recent 90371.2008v1 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 Google Scholar Google Scholar Articles by Legrand, M. Articles by Ince, C. Search for Related Content PubMed PubMed Citation Articles by Legrand, M. Articles by Ince, C.

L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats

Matthieu Legrand,^1,2,* Emre Almac,^1,* Egbert G. Mik,³ Tanja Johannes,⁴ Asl Kandil,⁵ Rick Bezemer,¹ Didier Payen,² and Can Ince¹

¹Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; ²Department of Anesthesiology and Critical Care, Lariboisière Hospital, Assistance Publique-Hopitaux de Paris; University of Paris, Paris, France; ³Department of Anesthesiology, Erasmus Medical Center, University of Rotterdam, Rotterdam, The Netherlands; ⁴Department of Anesthesiology and Critical Care, University Hospital Tuebingen, Tuebingen, Germany; and ⁵Department of Biology, Istanbul University, Faculty of Science, Istanbul, Turkey

Submitted 16 June 2008 ; accepted in final form 13 February 2009

Even though renal hypoxia is believed to play a pivotal role in the development of acute kidney injury, no study has specifically addressed the alterations in renal oxygenation in the early onset of renal ischemia-reperfusion (I/R). Renal oxygenation depends on a balance between oxygen supply and consumption, with the nitric oxide (NO) as a major regulator of microvascular oxygen supply and oxygen consumption. The aim of this study was to investigate whether I/R induces inducible NO synthase (iNOS)-dependent early changes in renal oxygenation and the potential benefit of iNOS inhibitors on such alterations. Anesthetized Sprague-Dawley rats underwent a 30-min suprarenal aortic clamping with or without either the nonselective NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) or the selective iNOS inhibitor L-N⁶-(1-iminoethyl)lysine hydrochloride (L-NIL). Cortical (CµPO₂) and outer medullary (MµPO₂) microvascular oxygen pressure (µPO₂), renal oxygen delivery (DO_2ren), renal oxygen consumption (O_2ren), and renal oxygen extraction (O₂ER) were measured by oxygen-dependent quenching phosphorescence techniques throughout 2 h of reperfusion. During reperfusion renal arterial resistance and oxygen shunting increased, whereas renal blood flow, CµPO₂, and MµPO₂ (–70, –42, and –42%, respectively, P < 0.05), O_2ren, and DO_2ren (–70%, P < 0.0001, and –28%, P < 0.05) dropped. Whereas L-NAME further decreased DO_2ren, O_2ren, CµPO₂, and MµPO₂ and deteriorated renal function, L-NIL partially prevented the drop of DO_2ren and µPO₂, increased O₂ER, restored O_2ren and metabolic efficiency, and prevented deterioration of renal function. Our results demonstrate that renal I/R induces early iNOS-dependent microvascular hypoxia in disrupting the balance between microvascular oxygen supply and O_2ren, whereas endothelial NO synthase activity is compulsory for the maintenance of this balance. L-NIL can prevent ischemic-induced renal microvascular hypoxia.

acute kidney injury; nitric oxide; microcirculation