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Oxidative/Carbonyl Stress in the Renal Circulation and Cardiovascular Renal Injury

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Studies on Renal Disorders

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Abstract

Both clinical and animal studies have demonstrated that oxidative and carbonyl stress are involved in the pathogenesis of hypertension, diabetes, and chronic kidney disease (CKD). Not only does direct biochemical action cause renal injury, but oxidative/carbonyl stress also participates in the physiological role on sodium homeostasis and regulation of blood pressure. The physiological role of oxidative stress relies on the balance between nitric oxide (NO) and reactive oxygen species (ROS). The balance between NO and ROS regulates renal medullary circulation and regulates blood pressure. In physiological conditions, NO is largely produced in the tubules and diffuses into the surrounding capillaries such as the vasa recta. These NO can be counter-balanced by the ROS produced in the tubules of renal medulla such as the medullary thick ascending limb. This tubulovascular NO crosstalk in the medulla regulates medullary blood flow (MBF). Reduction of MBF with reduction of NO and increased ROS increases sodium reabsorption and thereby develops hypertension. This is one of the mechanisms of salt-sensitive hypertension seen in Dahl-salt sensitive rats. Since oxygen tension of renal medulla is flow limited, reduction of renal MBF induces hypoxia as well as ischemia. Therefore, the outer medulla is an early target for enhanced oxidative stress, such as in hypertension and diabetes. Enhanced oxidative/carbonyl stress is also involved in insulin sensitivity, which is a key pathogenesis of CKD and metabolic syndrome. An increase in renal perfusion pressure results in the enhanced expression of molecules related to oxidative stress, inflammation, and wound healing. These mechanisms had an advantage for lifestyle in ancient days but have become a silent killer in modern culture. This paradigm shift of antiaging could explain why oxidative/carbonyl stress is enhanced in modern lifestyle diseases.

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Acknowledgments

We thank Yoshimi Yoneki, Hiroko Ito, and Kiyomi Kisu for their expert technical assistance.

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Authors and Affiliations

  1. Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryocho, Aoba-ku, Sendai, 980-8574, Japan

    Takefumi Mori

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  1. Takefumi Mori
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  2. Toshio Miyata
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  3. Sadayoshi Ito
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Correspondence to Takefumi Mori .

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Editors and Affiliations

  1. Graduate School of Medicine, Division of Molecular Medicine and Thera, Tohoku University, Seiryo-machi 2-1, Sendai, 980-8575, Japan

    Toshio Miyata

  2. Medizinische Klinik IV, Universitätsklinikum Erlangen, Krankenhausstr. 12, Erlangen, 91054, Germany

    Kai-Uwe Eckardt

  3. Graduate School of Medicine &, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Tokyo, 113-8655, Japan

    Masaomi Nangaku

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Mori, T., Miyata, T., Ito, S. (2011). Oxidative/Carbonyl Stress in the Renal Circulation and Cardiovascular Renal Injury. In: Miyata, T., Eckardt, KU., Nangaku, M. (eds) Studies on Renal Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press. https://doi.org/10.1007/978-1-60761-857-7_15

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