Iloprost preserves renal oxygenation and restores kidney function in endotoxemia-related acute renal failure in the rat


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Abstract

Objective:To investigate that exogenous prostacyclin would counterbalance an endotoxemia-induced intrarenal vasoconstriction and would therefore have beneficial effects on kidney function.Design:Prospective, randomized, controlled study.Setting:University medical center research laboratory.Subjects:Eighteen male Wistar rats.Interventions:In anesthetized and ventilated animals, arterial blood pressure (mean arterial blood pressure [MAP]) and renal blood flow (RBF) were recorded. Renal microvascular Po2 (μPo2) and renal venous Po2 were continuously measured by phosphorescence lifetime technique. All animals received a 30-minute infusion of lipopolysaccharide (LPS) (2.5 mg/kg) to induce endotoxemia. One group of rats was not resuscitated. A second group received fluid resuscitation 90 minutes after stop of LPS infusion. In a third group of rats, the prostacyclin analogue iloprost (100 ng/kg/min) was continuously infused in addition to fluid resuscitation. Furthermore, in all the animals, plasma NOx levels, renal inducible nitric-oxide synthase (iNOS) messenger RNA (mRNA) expression, and creatinine clearance were determined.Measurements and Main Results:During LPS infusion, MAP and RBF progressively dropped to 50% of baseline at 120 minutes. After an initial increase in MAP and RBF, start of fluid resuscitation with iloprost resulted in the stabilization of both parameters. All animals became anuric during endotoxemia. Only in animals receiving iloprost was creatinine clearance totally restored at the end of the experiment. Iloprost had no significant effects on average μPo2, but prevented the occurrence of cortical microcirculatory hypoxic areas. NOx levels and iNOS mRNA expression were significantly increased in all animals receiving LPS after 5 hours. There was no difference in NOx concentration between the different groups. In animals receiving iloprost, iNOS mRNA expression was significantly suppressed in the inner medulla.Conclusions:Iloprost significantly restored kidney function of endotoxemic rats to baseline values. This beneficial effect of iloprost on renal function might be addressed to an improvement in intrarenal oxygenation.

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