羊脓毒症前肾髓质低灌注和低氧先于急性肾损伤(AKI)发生。氧化/亚硝酸化应激、炎症和受损的一氧化氮产生可能是这种病理生理的贡献因素。我们测试了抗氧化和抗炎药物tempol是否可以改变这些反应。在单侧肾切除后，我们在肾皮质和肾髓质中插入肾动脉导管和激光多普勒/氧敏感探针。未麻醉的羊静脉注射大肠杆菌，感染发生时静脉注射tempol(IVT; 30mg/kg/h)，肾动脉注射tempol(RAT; 3mg/kg/h)或车辆。给予车辆的脓毒症羊出现肾髓质低灌注(灌注下降了76±16%)、低氧(氧合下降70±13%)和AKI(肌酐清除率下降了87±8%)，IVT时相似变化。然而，RAT保护了髓质灌注(1072±307到1005±271单位)、氧合(46±8到43±6mmHg)和肌酐清除率(61±10到66±20mL/min)。血浆、肾髓质和皮质组织马来烷醛和髓质3-硝基酪氨酸在脓毒症中明显降低，但不受IVT或RAT的影响。与氧化/亚硝酸化应激标志物降低一致，皮质和髓质核因子红细胞相关因子2明显增加，且不受IVT或RAT的影响。然而，RAT防止了脓毒症诱导的皮质组织肿瘤坏死因子α(TNF-α)过表达(下降51±16%)和髓质内皮一氧化氮合酶(eNOS)的Thr-495磷酸化(下降63±18%)。在羊阴性革兰氏菌脓毒症中，肾动脉注射tempol预防了肾髓质低灌注、低氧和AKI，并降低了TNF-α的表达和eNOS的非耦联。然而，它不影响氧化/亚硝酸化应激标志物，这在阴性革兰氏菌脓毒症中明显降低。© 2023作者。Acta Physiologica由斯堪的纳维亚生理学会代表John Wiley & Sons Ltd出版。

Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant and anti-inflammatory drug, tempol, may modify these responses.Following unilateral nephrectomy, we inserted renal arterial catheters and laser-Doppler/oxygen-sensing probes in the renal cortex and medulla. Noanesthetized sheep were administered intravenous (IV) Escherichia coli and, at sepsis onset, IV tempol (IVT; 30 mg kg-1  h-1 ), renal arterial tempol (RAT; 3 mg kg-1  h-1 ), or vehicle.Septic sheep receiving vehicle developed renal medullary hypoperfusion (76 ± 16% decrease in perfusion), hypoxia (70 ± 13% decrease in oxygenation), and AKI (87 ± 8% decrease in creatinine clearance) with similar changes during IVT. However, RAT preserved medullary perfusion (1072 ± 307 to 1005 ± 271 units), oxygenation (46 ± 8 to 43 ± 6 mmHg), and creatinine clearance (61 ± 10 to 66 ± 20 mL min-1 ). Plasma, renal medullary, and cortical tissue malonaldehyde and medullary 3-nitrotyrosine decreased significantly with sepsis but were unaffected by IVT or RAT. Consistent with decreased oxidative/nitrosative stress markers, cortical and medullary nuclear factor-erythroid-related factor-2 increased significantly and were unaffected by IVT or RAT. However, RAT prevented sepsis-induced overexpression of cortical tissue tumor necrosis factor alpha (TNF-α; 51 ± 16% decrease; p = 0.003) and medullary Thr-495 phosphorylation of endothelial nitric oxide synthase (eNOS; 63 ± 18% decrease; p = 0.015).In ovine Gram-negative sepsis, renal arterial infusion of tempol prevented renal medullary hypoperfusion and hypoxia and AKI and decreased TNF-α expression and uncoupling of eNOS. However, it did not affect markers of oxidative/nitrosative stress, which were significantly decreased by Gram-negative sepsis.© 2023 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.