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Abstract: SA-PO1103

Loss of Urine Concentration and Subsequent Dehydration Characterizes Hypertension in Rats with Chronic Renal Failure

Session Information

  • Salt and Hypertension
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Hypertension

  • 1104 Hypertension: Clinical and Translational - Salt and Hypertension


  • Kovarik, Johannes J., Vanderbilt University, Nashville, Tennessee, United States
  • Kitada, Kento, Kagawa University, Kagawa, Japan
  • Marton, Adriana, Vanderbilt University, Nashville, Romania
  • Daub, Steffen, Department of Clinical Pharmacology, Vanderbilt University Medial Center, Nashville, Tennessee, United States
  • Zhang, Yahua, Vanderbilt University, Nashville, Romania
  • Pedchenko, Tetyana, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Zhao, Yan, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Klein, Janet D., Emory University, Atlanta, Georgia, United States
  • Bailey, James L., Emory University School of Medicine, Atlanta, Georgia, United States
  • Cordasic, Nada, University Hospital of Erlangen, Erlangen, Germany
  • Hilgers, Karl F., University of Erlangen, Erlangen, Germany
  • Sands, Jeff M., Emory University Renal Division, Atlanta, Georgia, United States
  • Nishiyama, Akira, Kagawa University Medical School, Kita-Gun, Japan
  • Titze, Jens, Vanderbilt University, Nashville, Romania

The pressure-natriuresis concept suggests that blood pressure-driven increase in renal salt excretion in parallel normalizes the extracellular volume (ECV). In contrast to this traditional view, we have recently shown, that the biological principle of renal salt excretion is urea-driven ECV control by the renal concentration mechanism. We tested the hypothesis, whether hypertension in rats with experimental renal failure (5/6Nx) is characterized by body water loss due to an inability to concentrate the urine.


We investigated urine flow, osmolyte excretion, urine concentration, arterial blood pressure, and hepatic and extrahepatic urea generation in 5/6Nx (n=23; renal mass ablation) and sham-operated (n=19) Sprague-Dawley rats.


7 weeks after renal mass ablation, 5/6Nx rats increased their arterial blood pressure by 24.4±20.1 mmHg (P<0.05). Hypertensive 5/6Nx rats showed dehydration with a 13.8±7.0 mOsm/kg increase in plasma osmolality (P<0.001) and reduced ability to concentrate the urine (urine osmolality reduced by -771±590 mOsm/kg; P<0.001). In anesthetized animals, we found a direct relationship between 2Na+2K+Urea osmolyte excretion and urine flow (y=1.24x-3.3; R2=0.75), indicating osmotic diuresis. 5/6Nx rats showed pronounced 2Na+2K+Urea osmolyte loss (+13.2±5.1 mmol/d) with predominant urea loss (+13.4±4.9 mmol/d) which increased the urine volume by +19.5±7.4 ml/d (all P<0.001) and was paralleled by only discrete Na+ loss and K+ retention. In conscious 5/6Nx rats, the urea-driven loss of the renal concentration ability was coupled with a +37.9±15.1 ml/d increase in free-water clearance, indicating renal water loss. The renal urea leak resulted in compensatory increases in urea osmolyte generation in skeletal muscle (arginase activity: +8.7±6.7 units/L/kg, P<0.05; urea content: +1.9±1.2, P<0.01) in 5/6Nx rats.


Hypertension in a rat model of chronic renal failure is characterized by urea-driven loss of the renal concentration mechanism, which leads to increased renal water loss and extracellular volume contraction. Our findings indicate that sodium retention with subsequent volume overload is not the underlying cause of blood pressure increase in 5/6Nx rats.