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Article
Impairment of Na/K-ATPase Signaling in Renal Proximal Tubule Contributes to Dahl salt-sensitive Hypertension
Pharmaceutical Science and Research
  • Jiang Liu, Marshall University
  • Yanling Yan, Marshall University
  • Lijun Liu
  • Zijian Xie
  • Deepak Malhotra
  • Bina Joe
  • Joseph I. Shapiro
Document Type
Article
Publication Date
1-1-2011
Abstract
We have observed that, in renal proximal tubular cells, cardiotonic steroids such as ouabain in vitro signal through Na/K-ATPase, which results in inhibition of transepithelial 22Na transport by redistributing Na/K-ATPase and NHE3. In the present study, we investigate the role of Na/K-ATPase signaling in renal sodium excretion and blood pressure regulation in vivo. In Sprague-Dawley rats, high salt diet activated c-Src and induced redistribution of Na/K-ATPase and NHE3 in renal proximal tubules. In Dahl salt sensitive (S) and resistant (R) rats given high dietary salt, we found different effects on blood pressure but, more interestingly, different effects on renal salt handling. These differences could be explained by different signaling through the proximal tubular Na/KATPase. Specifically, in Dahl R rats, high salt diet significantly stimulated phosphorylation of c-Src and ERK1/2, reduced Na/K-ATPase activity and NHE3 activity, and caused redistribution of Na/K-ATPase and NHE3. In contrast, these adaptations were either much less effective or not seen in the Dahl S rats. We also studied the primary culture of renal proximal tubule isolated from Dahl S and R rats fed a low salt diet. In this system, ouabain induced Na/K-ATPase/c-Src signaling and redistribution of Na/K-ATPase and NHE3 in the Dahl R rats, but not in the Dahl S rats. Our data suggested that impairment of Na/K-ATPase signaling and consequent regulation of Na/K-ATPase and NHE3 in renal proximal tubule may contribute to salt-induced hypertension in the Dahl S rat.
Comments

The version of record is available at http://www.jbc.org/content/early/2011/05/09/jbc.M111.246249.full.pdf. Copyright © 2011 The American Society for Biochemistry and Molecular Biology, Inc. DOI 10.1074/jbc.M111.246249

Citation Information
Liu J, Yan Y, Liu L, Xie Z, Malhotra D, Joe B, Shapiro JI. (2011). Impairment of Na/K-ATPase signaling in renal proximal tubule contributes to Dahl salt-sensitive hypertension. Journal of Biological Chemistry 286(26):22806-13. PMID: 21555512