Increased renal oxygen consumption leads to hypoxia in sepsis‐associated acute kidney injury (890.9)

In experimental sepsis, the rapid development of renal medullary hypoxia precedes the development of acute kidney injury (AKI) and may contribute to its pathogenesis. We investigated whether inhibiting active sodium transport and oxygen consumption in the medullary thick ascending limb with furosemide attenuates the medullary hypoxia in experimental septic AKI. Sheep were instrumented with flow probes on the pulmonary and renal arteries and fiber optic probes to measure renal cortical and medullary perfusion and oxygen tension (Po2). Sepsis and AKI were induced by infusion of live Escherichia coli. At 24 h of sepsis there were significant decreases in renal medullary tissue perfusion (1,332 ± 233 to 698 ± 159 blood perfusion units) and Po2 (44 ± 6 to 19 ± 6 mmHg) (both P < 0.05). By 5 min after intravenous administration of furosemide (20 mg), renal medullary Po2 increased to 43 ± 6 mmHg and remained at this normal level for 8 h. Furosemide caused transient increases in fractional excretion of sodium and creatinine clearance, but medullary perfusion, renal blood flow, and renal oxygen delivery were unchanged. Urinary F2-isoprostanes, an index of oxidative stress, were not significantly changed at 24 h of sepsis but tended to transiently decrease after furosemide treatment. In septic AKI, furosemide rapidly restored medullary Po2 to preseptic levels. This effect was not accompanied by changes in medullary perfusion or renal oxygen delivery but was accompanied by a transient increase in fractional sodium excretion, implying decreased oxygen consumption as a mechanism.

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

AJP Renal Physiology ◽

10.1152/ajprenal.90371.2008 ◽

2009 ◽

Vol 296 (5) ◽

pp. F1109-F1117 ◽

Cited By ~ 52

Author(s):

Matthieu Legrand ◽

Emre Almac ◽

Egbert G. Mik ◽

Tanja Johannes ◽

Aslı Kandil ◽

...

Keyword(s):

Renal Function ◽

Oxygen Consumption ◽

Oxygen Supply ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

No Synthase ◽

Metabolic Efficiency ◽

Sprague Dawley ◽

Renal Oxygen Consumption ◽

Renal Oxygen

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, CμPo2, 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 Do2ren 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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