L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats
American Journal of Physiology - Renal Fluid and Electrolyte Physiology , Volume 296 - Issue 5
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 Nω-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 (DO2ren), renal oxygen consumption (V̇O2ren), 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, CμPO 2, and MμPO2 (-70, -42, and -42%, respectively, P < 0.05), V̇O2ren, and DO2ren (-70%, P < 0.0001, and -28%, P < 0.05) dropped. Whereas L-NAME further decreased DO2ren, V̇O2ren, CμPO2, and MμPO2 and deteriorated renal function, L-NIL partially prevented the drop of DO 2ren and μPO2, increased O2ER, restored V̇O2ren 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 V̇O2ren, whereas endothelial NO synthase activity is compulsory for the maintenance of this balance. L-NIL can prevent ischemic-induced renal microvascular hypoxia.
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|American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Legrand, M, Almac, E, Mik, E.G, Johannes, T, Kandil, A, Bezemer, R, … Ince, C. (2009). L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats. American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 296(5). doi:10.1152/ajprenal.90371.2008