scholarly journals Loss of NHERF-1 expression prevents dopamine-mediated Na-K-ATPase regulation in renal proximal tubule cells from rat models of hypertension: aged F344 rats and spontaneously hypertensive rats

2017 ◽  
Vol 313 (2) ◽  
pp. C197-C206 ◽  
Author(s):  
Michelle T. Barati ◽  
Corey J. Ketchem ◽  
Michael L. Merchant ◽  
Walter B. Kusiak ◽  
Pedro A. Jose ◽  
...  
Keyword(s):  
Animal Models ◽  
Proximal Tubule ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Proximal Tubule Cells ◽  
Spontaneously Hypertensive ◽  
Sodium Hydrogen Exchanger ◽  
Tubule Cells ◽  
Wistar Kyoto ◽  
F344 Rats

Dopamine decreases Na-K-ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA α1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA α1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells, dopamine decreases NHERF-1 association with NKA α1 but increases its association with D1R. However, it is not known whether NHERF-1 plays a role in dopamine-mediated NKA regulation in animal models of hypertension. We hypothesized that defective dopamine-mediated regulation of NKA results from the decrease in NHERF-1 expression in rat renal PTCs isolated from animal models of hypertension [spontaneously hypertensive rats (SHRs) and aged F344 rats]. To test this hypothesis, we isolated and cultured renal PTCs from 22-mo-old F344 rats and their controls, normotensive 4-mo-old F344 rats, and SHRs and their controls, normotensive Wistar-Kyoto (WKY) rats. The results demonstrate that in both hypertensive models (SHR and aged F344), NHERF-1 expression, dopamine-mediated phosphorylation of NKA, and ouabain-inhibitable K+ transport are reduced. Transfection of NHERF-1 into PTCs from aged F344 and SHRs restored dopamine-mediated inhibition of NKA. These results suggest that decreased renal NHERF-1 expression contributes to the impaired dopamine-mediated inhibition of NKA in PTCs from animal models of hypertension.

scholarly journals Activation of MAPKs in Proximal Tubule Cells From Spontaneously Hypertensive and Control Wistar-Kyoto Rats

Hypertension ◽  
2000 ◽  
Vol 35 (5) ◽  
pp. 1160-1166 ◽  
Author(s):  
Astrid Parenti ◽  
Xiao-Lan Cui ◽  
Ulrich Hopfer ◽  
Marina Ziche ◽  
Janice G. Douglas
Keyword(s):  
Proximal Tubule ◽  
Proximal Tubule Cells ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Tubule Cells ◽  
Wistar Kyoto ◽  
And Control

Abnormal regulation of renal proximal tubule Na(+)-K(+)-ATPase by G proteins in spontaneously hypertensive rats

1994 ◽  
Vol 267 (6) ◽  
pp. F1069-F1075 ◽  
Author(s):  
R. W. Gurich ◽  
R. E. Beach
Keyword(s):  
Atpase Activity ◽  
Proximal Tubule ◽  
G Proteins ◽  
Spontaneously Hypertensive Rats ◽  
Renal Proximal Tubule ◽  
Sodium Reabsorption ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Regulatory Pathways ◽  
Wistar Kyoto

Enhanced salt reabsorption by the kidney, which may arise from impaired regulation of proximal tubule Na(+)-K(+)-ATPase activity, has a central role in the pathogenesis of essential hypertension. Guanine nucleotide binding proteins (G proteins) are involved in many regulatory pathways and have been implicated in the regulation of proximal tubule Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity. The present study was designed to evaluate further the regulation of Na(+)-K(+)-ATPase activity by G proteins in proximal tubule suspensions from Wistar-Kyoto rats (WKY) and to determine whether such regulation is abnormal in spontaneously hypertensive rats (SHR). Cholera toxin (CTX) inhibited Na(+)-K(+)-ATPase activity by approximately 40% in WKY but had no effect on Na(+)-K(+)-ATPase activity in SHR. In WKY, pretreatment of tubules with pertussis toxin (PTX), followed by the application of dopamine, inhibited Na(+)-K(+)-ATPase activity significantly, compared with the inhibition produced by dopamine alone. In SHR, dopamine alone did not inhibit Na(+)-K(+)-ATPase activity. However, in the presence of PTX, dopamine inhibited Na(+)-K(+)-ATPase activity significantly. These studies indicate that the renal proximal tubule Na(+)-K(+)-ATPase in WKY is regulated by both a PTX- and CTX-sensitive G protein(s) and that this regulation is abnormal in SHR. Such a defect could cause enhanced sodium reabsorption in SHR and contribute to the pathogenesis of hypertension in this model.

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