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Salt-sensitive hypertension in mitochondrial superoxide dismutase deficiency is associated with intra-renal oxidative stress and inflammation

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Abstract

Background

Renal interstitial inflammation and oxidative stress are invariably present and play a key role in the pathogenesis of hypertension in experimental animals. Mitochondria are the major source of reactive oxygen species (ROS). ROS generated in the mitochondria are normally contained by the mitochondrial antioxidant system including manganese superoxide dismutase (MnSOD). We have previously shown that a high salt diet causes hypertension in MnSOD-deficient (MnSOD+/−) mice but not in wild-type mice. The present study was undertaken to determine the effect of a high salt diet on oxidative and inflammatory pathways in the kidneys of MnSOD+/− mice compared to the wild-type mice.

Methods

Wild-type (MnSOD+/+) and MnSOD+/− mice were randomized to receive a regular or a high salt diet for 4 months. Tail arterial pressure was measured and timed urine collection was obtained. The animals were then euthanized and the kidneys were harvested and processed for histological examination and Western blot analyses.

Results

In confirmation of our earlier study, a high salt diet resulted in a significant rise in arterial pressure and urinary albumin excretion in MnSOD+/− mice. This was accompanied by upregulation of NAD(P)H oxidase subunits, activation of nuclear factor kappa B, and elevation of PAI-1, iNOS, oxidized LDL receptor, and CD36 in the kidneys of the MnSOD+/− mice fed the high salt diet. In contrast, consumption of a high salt diet did not significantly alter blood pressure, urine protein excretion, or the measured oxidative and inflammatory mediators in the wild-type mice.

Conclusion

Salt-induced hypertension in MnSOD+/− mice is associated with activation of intra-renal inflammatory and ROS generating pathways.

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Acknowledgments

The MnSOD-deficient mice were generously provided by Dr. Douglas C. Wallace.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Division of Nephrology and Hypertension, University of California, Irvine, Irvine, CA, USA

    Kyubok Jin & Nosratola D. Vaziri

  2. Department of Internal Medicine, Inje University Haeundae Paik Hospital, 1435 Jwa-dong, Haeundae-gu, Busan, 612-030, Korea

    Kyubok Jin

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  1. Kyubok Jin
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  2. Nosratola D. Vaziri
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Correspondence to Kyubok Jin.

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Jin, K., Vaziri, N.D. Salt-sensitive hypertension in mitochondrial superoxide dismutase deficiency is associated with intra-renal oxidative stress and inflammation. Clin Exp Nephrol 18, 445–452 (2014). https://doi.org/10.1007/s10157-013-0851-3

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  • DOI: https://doi.org/10.1007/s10157-013-0851-3

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