Kidney Week

Abstract: FR-PO316

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

Session Information

• Hypertension and CVD: Mechanisms - I
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

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

Yanling Yan,

• Chaudhry, Muhammad A., Marshall University School of Medicine, Huntington, West Virginia, United States

Muhammad A. Chaudhry,

• Nie, Ying, Marshall University, Huntington, West Virginia, United States

Ying Nie,

• Sun, Shuyan, Shijiangzhuang Medical School, Proctorville, Ohio, United States

Shuyan Sun,

• Bai, Fang, Marshall University JCE School of Medicine, Huntington, West Virginia, United States

Fang Bai,

• Pratt, Rebecca, Marshall University School of Medicine, Huntington, West Virginia, United States

Rebecca Pratt,

• Brickman, Cameron, Marshall University JCESOM, Huntington, West Virginia, United States

Cameron Brickman,

• Sodhi, Komal, Marshall University Joan C. Edwards School of Medicine, Huntington, West Virginia, United States

Komal Sodhi,

• Kim, Jung Han, Marshall University School of Medicine, Huntington, West Virginia, United States

Jung Han Kim,

• Malhotra, Deepak K., The University of Toledo, Toledo, Ohio, United States

Deepak K. Malhotra,

• Xie, Zi-jian, Marshall University, Huntington, West Virginia, United States

Zi-jian Xie,

• Shapiro, Joseph I., Marshall University School of Medicine, Huntington, West Virginia, United States

Joseph I. Shapiro,

• Liu, Jiang, Marshall University JCE School of Medicine, Huntington, West Virginia, United States

Jiang Liu,

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