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Abstract: SA-PO1102

Na/K-ATPase Signaling as an Amplifier of Oxidative Stress Contributes to the Increased Salt Sensitivity of Obese Hypertension

Session Information

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

Category: Hypertension

  • 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

  • Yan, Yanling, Marshall University School of Medicine, Huntington, West Virginia, United States
  • Chaudhry, Muhammad A., Marshall University School of Medicine, Huntington, West Virginia, United States
  • Nie, Ying, Marshall University School of Medicine, Huntington, West Virginia, United States
  • Kim, Jung Han, Marshall University School of Medicine, Huntington, West Virginia, United States
  • Xie, Zi-jian, Marshall University School of Medicine, Huntington, West Virginia, United States
  • Shapiro, Joseph I., Marshall University School of Medicine, Huntington, West Virginia, United States
  • Liu, Jiang, Marshall University School of Medicine, Huntington, West Virginia, United States
Background

Na/K-ATPase acts as a receptor for reactive oxygen species (ROS) and amplifies ROS signaling, regulating renal sodium excretion (JBC, 2011&2013; JAHA, 2016). Whether or not these pathways are involved in the pathogenesis of obese hypertension due to impaired Na/K-ATPase signaling has not been investigated.

Methods

Blood pressures were measured using the tail-cuff method. Na/K-ATPase signaling activation was assessed in the kidney cortex from high fat (HF)-induced obese C57BL/6J (B6) mice, polygenic obese TALLYHO/JngJ (TH) mice and obese Zucker rats by measuring the phosphorylation of c-Src and ERK1/2 by Western blot. Protein carbonylation (DNP) and heme oxygenase 1 (HO-1) as a commonly used marker for oxidative stress were used to measure the levels of ROS. Renal function curve was constructed with high salt diets (HS, 2, 4, and 8% NaCl).

Results

In the kidney cortex tissue, the Na/K-ATPase signaling (c-Src and ERK1/2 phosphorylation) and oxidative stress (protein carbonylation and HO-1) were activated and were not stimulated by HS diets in obese TH mice (comparing to B6 mice, Figure A, left panel). Moreover, in salt-loading experiments (with 2, 4, and 8% NaCl), we demonstrated that obese TH mice exhibited an increased salt sensitivity of blood pressure, characterized by a right-shifted, reduced slope in renal function curve (Figure A, right panel, p<0.01). We also observed had a higher baseline oxidative stress and Na/K-ATPase activation in Obese Zucker rats (comparing to lean Zucker rats, Figure B) and high fat-induced obese B6 mice.

Conclusion

Na/K-ATPase signaling activation as a commonly featured characteristic in obese mice and rat was implicated in the increased salt sensitivity of obese hypertension. Further studies targeting Na/K-ATPase signaling will explore the potential nodes for therapeutic intervention and precise target localization to render the required pharmacologic therapy more effective, minimizing the need for medications.