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https://doi.org/10.1371/journal.pone.0041896
Title: | Oxidative stress-induced glomerular mineralocorticoid receptor activation limits the benefit of salt reduction in Dahl salt-sensitive rats | Authors: | Kitada K. Nakano D. Liu Y. Fujisawa Y. Hitomi H. Shibayama Y. Shibata H. Nagai Y. Mori H. Masaki T. Kobori H. Nishiyama A. |
Keywords: | eplerenone hydroethidine mineralocorticoid receptor paraquat protein p22 protein p22phox serum and glucocorticoid regulated kinase 1 tempol unclassified drug animal cell animal experiment animal tissue article blood pressure regulation controlled study Dahl salt sensitive rat genetic transcription glomerulus high sodium intake kidney injury male mesangium cell nonhuman oxidative stress podocyte protein function proteinuria receptor activation sodium restriction tissue level Adrenalectomy Aldosterone Animals Biological Markers Blood Pressure Cyclic N-Oxides Ethidium Feeding Behavior Genes, Reporter Immediate-Early Proteins Kidney Glomerulus Luciferases Male Mesangial Cells Mice Oxidative Stress Podocytes Protein-Serine-Threonine Kinases Proteinuria Rats Rats, Inbred Dahl Receptors, Mineralocorticoid Sodium Chloride, Dietary Sodium-Hydrogen Antiporter Spin Labels Systole Time Factors Rattus |
Issue Date: | 2012 | Publisher: | Public Library of Science | Citation: | Kitada K., Nakano D., Liu Y., Fujisawa Y., Hitomi H., Shibayama Y., Shibata H., Nagai Y., Mori H., Masaki T., Kobori H., Nishiyama A. (2012). Oxidative stress-induced glomerular mineralocorticoid receptor activation limits the benefit of salt reduction in Dahl salt-sensitive rats. PLoS ONE 7 (7) : e41896. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0041896 | Abstract: | Background: Mineralocorticoid receptor (MR) antagonists attenuate renal injury in salt-sensitive hypertensive rats with low plasma aldosterone levels. We hypothesized that oxidative stress causes MR activation in high-salt-fed Dahl salt-sensitive rats. Furthermore, we determined if MR activation persisted and induced renal injury, even after switching from a high- to a normal-salt diet. Methods and Findings: High-salt feeding for 4 weeks increased dihydroethidium fluorescence (DHE, an oxidant production marker), p22phox (a NADPH oxidase subunit) and serum and glucocorticoid-regulated kinase-1 (SGK1, an MR transcript) in glomeruli, compared with normal-salt feeding, and these changes persisted 4 weeks after salt withdrawal. Tempol treatment (0.5 mmol/L) during high-salt feeding abolished the changes in DHE fluorescence, p22phox and SGK1. Dietary salt reduction after a 4-week high-salt diet decreased both blood pressure and proteinuria, but was associated with significantly higher proteinuria than in normal control rats at 4 weeks after salt reduction. Administration of tempol during high-salt feeding, or eplerenone, an MR antagonist (100 mg/kg/day), started after salt reduction, recovered proteinuria to normal levels at 4 weeks after salt reduction. Paraquat, a reactive oxygen species generator, enhanced MR transcriptional activity in cultured rat mesangial cells and mouse podocytes. Conclusions: These results suggest that oxidative stress plays an important role in glomerular MR activation in Dahl salt-sensitive rats. Persistent MR activation even after reducing salt intake could limit the beneficial effects of salt restriction. © 2012 Kitada et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/165569 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0041896 |
Appears in Collections: | Elements Staff Publications |
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