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Activation of the Renin-Angiotensin System and Chronic Hypoxia of the Kidney
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  • Published: 01 February 2008

Activation of the Renin-Angiotensin System and Chronic Hypoxia of the Kidney

  • Masaomi Nangaku1 &
  • Toshiro Fujita1 

Hypertension Research volume 31, pages 175–184 (2008)Cite this article

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Abstract

Recent studies emphasize the role of chronic hypoxia in the kidney as a final common pathway to end-stage renal failure (ESRD). Hypoxia of tubular cells leads to apoptosis or epithelial-mesenchymal transdifferentiation, which in turn exacerbates the fibrosis of the kidney with the loss of peritubular capillaries and subsequent chronic hypoxia, setting in train a vicious cycle whose end-point is ESRD. While fibrotic kidneys in an advanced stage of renal disease are devoid of peritubular capillary blood supply and oxygenation to the corresponding region, imbalances in vasoactive substances can cause chronic hypoxia even in the early phase of kidney disease. Among various vasoactive substances, local activation of the renin-angiotensin system (RAS) is particularly important because it can lead to the constriction of efferent arterioles, hypoperfusion of postglomerular peritubular capillaries, and subsequent hypoxia of the tubulointerstitium in the downstream compartment. In addition, angiotensin II induces oxidative stress via the activation of NADPH oxidase. Oxidative stress damages endothelial cells directly, causing the loss of peritubular capillaries, and also results in relative hypoxia due to inefficient cellular respiration. Thus, angiotensin II induces renal hypoxia via both hemodynamic and nonhemodynamic mechanisms. In the past two decades, considerable gains have been realized in retarding the progression of chronic kidney disease by emphasizing blood pressure control and blockade of the RAS. Chronic hypoxia in the kidney is an ideal therapeutic target, and the beneficial effects of blockade of RAS in kidney disease are, at least in part, mediated by the amelioration of local hypoxia.

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  1. Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan

    Masaomi Nangaku & Toshiro Fujita

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  1. Masaomi Nangaku
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  2. Toshiro Fujita
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Correspondence to Masaomi Nangaku.

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Nangaku, M., Fujita, T. Activation of the Renin-Angiotensin System and Chronic Hypoxia of the Kidney. Hypertens Res 31, 175–184 (2008). https://doi.org/10.1291/hypres.31.175

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  • Received: 09 May 2007

  • Accepted: 13 August 2007

  • Issue date: 01 February 2008

  • DOI: https://doi.org/10.1291/hypres.31.175

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Keywords

  • ischemia
  • chronic kidney disease
  • angiotensin receptor blocker
  • oxidative stress

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