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

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.

Abstract 221: Lost Adiponectin-induced Renal Sodium Excretion in Hypertension

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
hefei Huang ◽  
Yu Han ◽  
Zhen Wang ◽  
chunyu Zeng
Keyword(s):  
Atpase Activity ◽  
Proximal Tubule ◽  
Sodium Excretion ◽  
Inhibitory Effect ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cells ◽  
Wistar Kyoto Rats ◽  
Tubule Cells ◽  
Wistar Kyoto ◽  
Renal Proximal Tubule Cells

Obesity related hypertensive patients are often with impaired sodium excretion. However,the mechanisms are not clear. Adipocytes secrete numerous hormones, among which adiponectin is an important one. Adiponectin KO mice developed hypertension when maintained on a high-salt diet. In hypertensive patients, the plasma adiponectin levels are lower; there is relationship between lower serum adiponectin and new-onset hypertension.We hypothesize that adiponectin induces natriuresis and diuresis, the impaired adiponectin-induced sodium excretion might be involved in hypertension. Our present study found the expressions of both adiponectin (AdipoR1 and AdipoR2) receptor in kidney from Wistar-Kyoto rats. Infusion of adiponectin via supra-renal artery induces natriuresis and diuresis in Wistar-Kyoto rats. Treatment with adiponectin inhibited Na + -K + -ATPase activity in renal proximal tubule cells of Wistar-Kyoto rats. The inhibitory effect was mainly via AdipoR2 receptor, because the siRNA of AdipoR2, not AdipoR1,completely blocked the effect of adiponectin. In the presence of inhibitor for AMPK (compound C) or eNOS (L-NAME), the inhibitory effect of adiponectin on Na+-K+-ATPase activity was blocked, indicating AMPK-NO pathway is involved in the signaling pathway. In spontaneous hypertension rats, adiponectin-induced natriuresis and diuresis were lost;similarly, the inhibitory effect on Na+-K+-ATPase activity was also lost in renal proximal tubule cells of spontaneously hypertension rats. The impaired adiponectin effect might be ascribed to lower AdipoR2 expression in renal proximal tubule cells od spontaneously hypertension rats, because transfected with AdipoR2 reversed the inhibitory effect on Na+-K+-ATPase activity. These datas suggested that adiponection, via AdipoR2,induces natriuresis and diuresis; the impaired adiponectin function might be involved in the pathogenesis of hypertension.

scholarly journals Immortalization and characterization of proximal tubule cells derived from kidneys of spontaneously hypertensive and normotensive rats

1996 ◽  
Vol 50 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Philip G. Woost ◽  
David E. Orosz ◽  
Wenwu Jin ◽  
Phyllis S. Frisa ◽  
James W. Jacobberger ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Proximal Tubule Cells ◽  
Spontaneously Hypertensive ◽  
Tubule Cells

Dipeptide-induced Cl−secretion in proximal tubule cells

1997 ◽  
Vol 273 (5) ◽  
pp. C1623-C1631 ◽  
Author(s):  
Wenwu Jin ◽  
Ulrich Hopfer
Keyword(s):  
Proximal Tubule ◽  
Spontaneously Hypertensive Rat ◽  
Intact Cell ◽  
Ph Dependence ◽  
Primary Cultures ◽  
Electrical Current ◽  
Proximal Tubule Cell ◽  
Proximal Tubule Cells ◽  
Tubule Cells ◽  
Wistar Kyoto

During a survey of dipeptides that might be transported by the renal PEPT2 transporter in proximal tubule cells, we discovered that acidic dipeptides could stimulate transient secretory anion current and conductance increases in intact cell monolayers. The stimulatory effect of acidic dipeptides was observed in several proximal tubule cell lines that have been recently developed by immortalization of early proximal tubule primary cultures from the Wistar-Kyoto and spontaneously hypertensive rat strains and humans, suggesting that this phenomenon is a characteristic of proximal tubule cells. The electrical current induced in intact monolayers by Ala-Asp, a representative of these acidic dipeptides, must represent Cl− secretion rather than Na+ or H+ absorption, because 1) it was Na+ independent, 2) it showed a pH dependence different from that of the PEPT2 cotransporter, and 3) it correlated with an Ala-Asp-induced increase in Cl− conductance of the apical membrane in basolaterally amphotericin B-permeabilized monolayers. The secretory current could be inhibited by stilbene disulfonates, but not diphenylamine-2-carboxylates, suggesting a non-cystic fibrosis transmembrane conductance regulator type of Cl− conductance. The effect of Ala-Asp was dose dependent, with an apparent 50% effective concentration of ∼1 mM. Ala-Asp also produced intracellular acidification, suggesting that acidic dipeptides are also substrates for an H+-peptide cotransporter.

Na+/H+ exchanger activity and phosphorylation in temperature-sensitive immortalized proximal tubule cell lines derived from the spontaneously hypertensive rat

2000 ◽  
Vol 98 (4) ◽  
pp. 409-418 ◽  
Author(s):  
Leong L. NG ◽  
Sonja JENNINGS ◽  
Joan E. DAVIES ◽  
Paulene A. QUINN
Keyword(s):  
Proximal Tubule ◽  
Cell Lines ◽  
Western Blotting ◽  
Spontaneously Hypertensive Rat ◽  
Proximal Tubule Cell ◽  
Permissive Temperature ◽  
Proximal Tubule Cells ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Tubule Cells

Freshly isolated proximal tubules from the spontaneously hypertensive rat (SHR) demonstrate elevated Na+/H+ exchanger (NHE) activity, but the underlying mechanism is unclear. Because of the difficulties in preparing sufficient numbers of proximal tubule cells for detailed biochemical studies, we have generated cell lines from SHR and Wistar–Kyoto rat (WKY) proximal tubule cells. Cell lines were obtained by transforming the cells with an origin-defective mutant of simian virus 40 encoding a heat-labile T antigen (tsA58 transformant). Such cells proliferate at the permissive temperature of 33 °C, but growth is abolished at the restrictive temperature of 39 °C. The predominant NHE isoform expressed was isoform 1, as determined by sensitivity to HOE-694 (3-methylsulphonyl-4-piperidinobenzoyl guanidine) and Western blotting using specific polyclonal antisera to NHE-1. NHE-3 protein was also present. Northern blots of poly(A) mRNA extracts of the cell lines revealed a low abundance of transcripts for NHE-2, -3 and -4, with no systematic difference between the lines. Although the intracellular pH was similar in the SHR and WKY lines, HOE-694-sensitive H+ efflux due to NHE-1 was substantially elevated in SHR lines compared with WKY lines (95.0±2.8 and 39.9±5.7 mmol·min-1·l-1 respectively; P < 0.001; n = 6). H+ efflux due to non-Na+-dependent mechanisms were similar in lines from the two strains. Western blotting revealed that NHE-1 density was also very similar in SHR and WKY lines, and subcellular fractionation of homogenates indicated that NHE-1 was localized predominantly to plasma membranes. Thus the turnover number of NHE-1 was increased. Immunoprecipitation of 32P-labelled phosphoproteins from these lines demonstrated an approximately 2-fold higher degree of phosphorylation of NHE-1 in SHR compared with WKY lines. These cell lines form a useful model for defining the biochemical mechanisms leading to the NHE-1 phenotype in the SHR kidney, in addition to investigations of other SHR phenotypic markers.

Sign in / Sign up

Export Citation Format

Share Document