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

Legrand M., Almac E., Mik E. G., Johannes T., Kandil A., Bezemer R., ...Daha Fazla

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, cilt.296, sa.5, 2009 (SCI-Expanded) identifier identifier identifier

Özet

Legrand M, Almac E, Mik EG, Johannes T, Kandil A, Bezemer R, Payen D, Ince C. L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats. Am J Physiol Renal Physiol 296: F1109-F1117, 2009. First published February 18, 2009; doi:10.1152/ajprenal.90371.2008.-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-omega-nitro-L-arginine methyl ester (L-NAME) or the selective iNOS inhibitor L-N-6-(1-iminoethyl) lysine hydrochloride (L-NIL). Cortical (C mu Po-2) and outer medullary (M mu Po-2) microvascular oxygen pressure (mu Po-2), renal oxygen delivery (Do(2ren)), renal oxygen consumption ((V) over doto(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, C mu Po-2, and M mu Po-2 (-70, -42, and -42%, respectively, P < 0.05), (V) over dot o(2ren), and Do(2ren) (-70%, P < 0.0001, and -28%, P < 0.05) dropped. Whereas L-NAME further decreased Do(2ren), (V) over dot o(2ren), C mu Po-2, and M mu Po-2 and deteriorated renal function, L-NIL partially prevented the drop of Do(2ren) and mu Po-2, increased O2ER, restored (V) over dot 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 (V) over dot o(2ren), whereas endothelial NO synthase activity is compulsory for the maintenance of this balance. L-NIL can prevent ischemic-induced renal microvascular hypoxia.

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(omega)-nitro-L-arginine methyl ester (L-NAME) or the selective iNOS inhibitor L-N(6)-(1-iminoethyl)lysine hydrochloride (L-NIL). Cortical (CmicroPo(2)) and outer medullary (MmicroPo(2)) microvascular oxygen pressure (microPo(2)), renal oxygen delivery (Do(2ren)), renal oxygen consumption (Vo(2)(ren)), and renal oxygen extraction (O(2)ER) 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, CmicroPo(2), and MmicroPo(2) (-70, -42, and -42%, respectively, P < 0.05), Vo(2)(ren), and Do(2ren) (-70%, P < 0.0001, and -28%, P < 0.05) dropped. Whereas L-NAME further decreased Do(2ren), Vo(2)(ren), CmicroPo(2), and MmicroPo(2) and deteriorated renal function, L-NIL partially prevented the drop of Do(2ren) and microPo(2), increased O(2)ER, restored Vo(2)(ren) 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 Vo(2)(ren), whereas endothelial NO synthase activity is compulsory for the maintenance of this balance. L-NIL can prevent ischemic-induced renal microvascular hypoxia.