Distant effects of unilateral renal ischemia/reperfusion on contralateral kidney but not lung in rats: the roles of ROS and iNOS

Abstract

Keyword:Acute kidney injury, inducible nitric oxide synthase, reactive oxygen species, unilateral nephrectomy, unilateral renal ischemia https://mc06.manuscriptcentral.com/cjpp-pubs AbstractAcute kidney injury is usually associated with distant organ dysfunction. The roles of inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in this phenomenon were investigated following 2-h unilateral renal ischemia and 24-h reperfusion. There were three groups of rats subjected to either unilateral ischemia/reperfusion (UIR group), unilateral nephrectomy (UNX group), or shamoperation. Two further groups were given α-tocopherol and aminoguanidine with UIR (treated-UIR group) and UNX (treated-UNX group). Plasma nitrite/nitrate and malondialdehyde were elevated only in the UIR group. Creatinine clearance and blood flow increased in non-ischemic kidney of the UIR, but not to the same extent as remnant kidney of the UNX group, while they had equal compensatory rises in absolute Na + -and K + -excretion and urine flow. Non-ischemic kidney of the treated-UIR group, but not remnant kidney of the treated-UNX group, showed more elevation in blood flow, whereas both kidneys had reductions in absolute Na + -excretion and urine flow.Respiratory functional variable were not different between all groups. Therefore, 2-h unilateral renal ischemia and 24-h reperfusion did not affect lung but had distant effects on contralateral kidney partly mediated by ROS and NO-derived from iNOS to dampen compensatory increases in renal hemodynamics and to decrease tubular reabsorption.Keywords: Acute kidney injury, acute lung injury, alpha-tocopherol, aminoguanidine, inducible nitric oxide synthase, ischemia/reperfusion, reactive oxygen species, unilateral nephrectomy, unilateral renal ischemia.

Renal ischemia/reperfusion against nephrectomy for induction of acute lung injury in rats

“…In addition, co-treatment with a-tocopherol, as a potent antioxidant, and aminoguanidine, as an iNOS inhibitor, prevented the rises in plasma MDA and nitrite/nitrate and the fall in P a O 2 /F i O 2 following UIR. 20 Hence, there can be the possibility that the elevated plasma ROS and NO in the UIR group may affect lung to promote moderate interstitial infiltration of neutrophils that slightly reduces P a O 2 /F i O 2 . Of course, the increased infiltration of neutrophils into the lung interstitium of the UIR group was not accompanied with their migration into alveolar space as well as elevated interstitial and alveolar macrophages and, therefore, was not able to induce any pulmonary histological damage.…”

“…Meanwhile, the pressure of airways was measured during expiration by a pressure transducer connected to the PowerLab, and airway resistance was calculated by dividing airway pressure to the specified and constant air flow. 20,21 Then, each group was subdivided into three different subgroups of n ¼ 5 for (A) studying pulmonary performance at ex vivo condition in an isolated-perfused lung model, (B) obtaining bronchoalveolar lavage fluid (BALF), and also determining lung wet-to-dry weight ratio, and (C) removing kidneys and lungs for histopathological examination.…”

“…The remainder of BALF was centrifuged at 1500 rpm for 10 min at 4 C, and the supernatant was removed. The BALF supernatant together with a plasma sample, which had been obtained from the rat before taking BALF, were stored at À20 C. 20,26 Protein concentrations of the samples were measured by the Bradford method and presented as the ratio of BALF to plasma protein concentrations Â1000 ([Pr] BALF /[Pr] P Â 1000).…”

“…In the plasma samples, the content of MDA was determined by thiobarbituric acid reactive substances (TBARS) assay and the levels of nitrite (NO 2 À ) and nitrate (NO 3 À ) were measured by Griess method. As previously described in detail, 20 the concentrations of MDA and total NO 2 À /NO 3 À in plasma samples were calculated as lmol/L with using a microplate reader (Synergy HT, BioTek Instruments, Winooski, VT).…”

“…On the other hand, we recently demonstrated that a 2-h unilateral renal ischemia and 24-h reperfusion had distant effect on the contralateral non-ischemic kidney to dampen its compensatory hyperperfusion and hyperfiltration, while the remnant kidney in the unilateral nephrectomy (UNX) model exhibited complete compensatory overfunction. 20 Therefore, this investigation was designed to study the links between AKI and ALI through evaluating pulmonary structural and functional parameters along with measuring plasma levels of reactive oxygen species (ROS), nitric oxide (NO), creatinine, urea, Na þ , K þ , and osmolality as well as arterial pH, HCO 3 À , O 2 and CO 2 tension, and blood pressure following induction of AKI by BIR, BNX, UIR, or UNX.…”