Abstract
BackgroundExtracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow.MethodsSepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated.ResultsAn increase in ECSOD content was associated with decreased 3-nitrotyrosine levels. These events were associated with an increase in pVASP content and maintenance of renal blood flow. Moreover, previous treatment with a SOD inhibitor increased nitrotyrosine content and reduced renal blood flow.ConclusionsECSOD appears to have a major role in decreasing peroxynitrite formation in the renal artery during the early stages of sepsis development, and its application can be important in renal blood flow control and maintenance during septic insult.
Highlights
Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury
To further evaluate the mechanisms involved in the preservation of renal blood flow, we analysed the content of phosphorylated vasodilator-stimulated phosphoprotein (pVASP), which increased at 6 and 12 h after sepsis induction (Fig. 6)
To determine whether this treatment truly interfered with SOD activity, we demonstrated that it induced a decrease in SOD activity but not in SOD protein content
Summary
Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. A large amount of reactive oxygen species (ROS) and nitric oxide (NO) are produced [3, 4]. In this context, superoxide radicals can react with NO to produce peroxynitrite [5, 6]. Since the production of peroxynitrite is associated with decreased renal blood flow and acute kidney injury [13, 14], ECSOD could play a major protective role in this context, but little is known about its modulation during sepsis
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