ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO316

Role of Na/K-ATPase Signaling in Susceptibility to Hypertension in Salt-Sensitive Animal Models

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Yan, Yanling, Marshall University, Joan C. Edwards 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, Huntington, West Virginia, United States
  • Sun, Shuyan, Shijiangzhuang Medical School, Proctorville, Ohio, United States
  • Bai, Fang, Marshall University JCE School of Medicine, Huntington, West Virginia, United States
  • Pratt, Rebecca, Marshall University School of Medicine, Huntington, West Virginia, United States
  • Brickman, Cameron, Marshall University JCESOM, Huntington, West Virginia, United States
  • Sodhi, Komal, Marshall University Joan C. Edwards School of Medicine, Huntington, West Virginia, United States
  • Kim, Jung Han, Marshall University School of Medicine, Huntington, West Virginia, United States
  • Malhotra, Deepak K., The University of Toledo, Toledo, Ohio, United States
  • Xie, Zi-jian, Marshall University, Huntington, West Virginia, United States
  • Shapiro, Joseph I., Marshall University School of Medicine, Huntington, West Virginia, United States
  • Liu, Jiang, Marshall University JCE School of Medicine, Huntington, West Virginia, United States
Background

Previous studies from our and our collaborative laboratories have indicated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure (JBC, 2011; JAHA, 2016). In the present work, the Na/K-ATPase signaling was investigated in the animal models of salt-sensitive hypertension.

Methods

Studies were conducted with tissues from rats and mice made hypertensive by the salt administration. Na/K-ATPase signaling including phosphorylation of c-Src and ERK1/2 and protein carbonylation (DNP, commonly used as a marker for ROS) was assessed by Western blot(WB). Renal function curve was constructed with high salt diets (HS, 2, 4, and 8% NaCl). Urinary and plasma Na+ levels were measured by flame photometry.

Results

In the Dahl salt-sensitive hypertensive rat (S), the renal proximal tubules (RPTs) contained significantly more protein carbonylation than did the control (Dahl salt-resistant rat, R) RPTs (Fig. A. NC, Normal chow). Qualitatively similar effects were observed on the Na/K-ATPase signaling from the kidney cortex of three obese rat and mouse models (Fig. B-D). As did Dahl S rat, (Fig. A and in JBC, 2011), Na/K-ATPase signaling was not able to be stimulated by HS (Fig. D), leading to blunted urinary Na+ excretion and salt-sensitive hypertension in obese TALLYHO/JngJ (TH) mice. More importantly, pNaKtide as an antagonist of Na/K-ATPase signaling attenuated protein carbonylation and c-Src phosphorylation stimulated by a high-fat diet (HF, Fig. C).

Conclusion

All four forms of salt-sensitive hypertension showed significant elevation of baseline Na/K-ATPase signaling when compared to their respective controls, indicating that this aberration in Na/K-ATPase signaling may represent a common signaling defect fundamental to the salt-sensitive hypertensive syndrome irrespective of etiology.

Funding

  • Other NIH Support