scholarly journals Glomerular tubular balance is suppressed in adenosine type 1 receptor-deficient mice

2010 ◽  
Vol 299 (5) ◽  
pp. F1158-F1163 ◽  
Author(s):  
Tracy D. Bell ◽  
Zaiming Luo ◽  
William J. Welch
Keyword(s):  
Proximal Tubule ◽  
Proximal Tubule Cells ◽  
Fluid Reabsorption ◽  
Volume Load ◽  
Fluid Uptake ◽  
Perfusate Flow ◽  
Sodium Hydrogen Exchanger ◽  
Acute Changes

Glomerular tubular balance maintains a stable fractional solute and fluid reabsorption in the proximal tubule over a range of glomerular filtration rates. The mediators of this process are unknown. We tested the hypothesis that adenosine, produced in proximal tubule cells acting on adenosine type 1 receptors (A1-AR) promotes Na+ and fluid uptake and mediates glomerular tubular balance. Absolute proximal fluid reabsorption ( Jv) was measured by in vivo microperfusion in A1-AR knockout and wild-type mice during perfusion of the closed proximal tubule at 2–10 nl/min. Jv increased with perfusate flow from 2–4 nl/min in both strains, but the fractional increase was lower in A1-AR−/− mice (A1-AR+/+: 114% vs. A1-AR−/−: 38%; P < 0.001), suggesting reduced glomerular tubular balance (GTB). At higher perfusion rates, Jv increased modestly in both strains, indicating less GTB at higher flow. The physiological effects of reduced GTB in A1-AR−/− mice were assessed from the response to an acute volume load (1 ml/2 min). Na+ excretion and urine flow increased 76 and 73% more in A1-AR−/− mice than A1-AR+/+ over the following 30 min, accompanied by a higher proximal tubule flow (A1-AR−/−: 6.9 ± 0.9 vs. A1-AR+/+: 5.2 ± 0.6 nl/min; P < 0.05). The expression of the sodium-hydrogen exchanger 3 and sodium phosphate cotransporter-2 were similar between strains. In conclusion, GTB is dependent on adenosine acting on type 1 receptors in the proximal tubule. This may contribute to acute changes in Na+ and fluid reabsorption.

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 Low dose ouabain stimulates Na K ATPase α1 subunit association with angiotensin II type 1 receptor in renal proximal tubule cells

2016 ◽  
Vol 1863 (11) ◽  
pp. 2624-2636 ◽  
Author(s):  
Corey J. Ketchem ◽  
Clayton D. Conner ◽  
Rebecca D. Murray ◽  
Madalyn DuPlessis ◽  
Eleanor D. Lederer ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Low Dose ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cells ◽  
Tubule Cells ◽  
Renal Proximal Tubule Cells ◽  
Α1 Subunit

scholarly journals Antenatal betamethasone attenuates the angiotensin-(1–7)-Mas receptor-nitric oxide axis in isolated proximal tubule cells

2017 ◽  
Vol 312 (6) ◽  
pp. F1056-F1062 ◽  
Author(s):  
Yixin Su ◽  
Jianli Bi ◽  
Victor M. Pulgar ◽  
Mark C. Chappell ◽  
James C. Rose
Keyword(s):  
Nitric Oxide ◽  
Proximal Tubule ◽  
Cell Model ◽  
Primary Cultures ◽  
Specific Effect ◽  
Renal Tubules ◽  
Proximal Tubule Cells ◽  
Mas Receptor ◽  
Tubule Cells

We previously reported a sex-specific effect of antenatal treatment with betamethasone (Beta) on sodium (Na+) excretion in adult sheep whereby treated males but not females had an attenuated natriuretic response to angiotensin-(1–7) [Ang-(1–7)]. The present study determined the Na+ uptake and nitric oxide (NO) response to low-dose Ang-(1–7) (1 pM) in renal proximal tubule cells (RPTC) from adult male and female sheep antenatally exposed to Beta or vehicle. Data were expressed as percentage of basal uptake or area under the curve for Na+ or percentage of control for NO. Male Beta RPTC exhibited greater Na+ uptake than male vehicle cells (433 ± 28 vs. 330 ± 26%; P < 0.05); however, Beta exposure had no effect on Na+ uptake in the female cells (255 ± 16 vs. 255 ± 14%; P > 0.05). Ang-(1–7) significantly inhibited Na+ uptake in RPTC from vehicle male (214 ± 11%) and from both vehicle (190 ± 14%) and Beta (209 ± 11%) females but failed to attenuate Na+ uptake in Beta male cells. Beta exposure also abolished stimulation of NO by Ang-(1–7) in male but not female RPTC. Both the Na+ and NO responses to Ang-(1–7) were blocked by Mas receptor antagonist d-Ala7-Ang-(1–7). We conclude that the tubular Ang-(1–7)-Mas-NO pathway is attenuated in males and not females by antenatal Beta exposure. Moreover, since primary cultures of RPTC retain both the sex and Beta-induced phenotype of the adult kidney in vivo they appear to be an appropriate cell model to examine the effects of fetal programming on Na+ handling by the renal tubules.

scholarly journals Low salt intake increases adenosine type 1 receptor expression and function in the rat proximal tubule

2008 ◽  
Vol 295 (1) ◽  
pp. F37-F41 ◽  
Author(s):  
Aaron Kulick ◽  
Carolina Panico ◽  
Pritmohinder Gill ◽  
William J. Welch
Keyword(s):  
Proximal Tubule ◽  
Salt Intake ◽  
Selective Inhibitor ◽  
Receptor Expression ◽  
Local Production ◽  
Low Salt ◽  
And Function ◽  
Rat Proximal Tubule

Adenosine mediates Na+ reabsorption in the proximal tubule (PT) and other segments by activating adenosine type 1 receptors (A1-AR). We tested the hypothesis that A1-AR in the PT is regulated by salt intake and participates in the kidney adaptation to changes in salt intake. Absolute fluid reabsorption ( Jv) was measured by direct in vivo microperfusion and recollection in rats maintained on low (LS; 0.03% Na, wt/wt)-, normal (NS; 0.3% Na)-, and high-salt (HS; 3.0% Na) diets for 1 wk. The effect of microperfusion of BG9719 a highly selective inhibitor of A1-ARs or adenosine deaminase (AD), which metabolizes adenosine, was measured in each group. Jv was higher in PT from LS rats (LA: 2.8 ± 0.2 vs. NS: 2.1 ± 0.2 nl·min−1·mm−1, P < 0.001). Jv in HS rats was not different from NS. BG9719 reduced Jv in LS rats by 66 ± 6% (LS: 2.8 ± 0.2 vs LS+CVT: 1.3 ± 0.3 nl·min−1·mm−1, P < 0.001), which was greater than its effect in NS (45 ± 4%) or HS (41 ± 4%) rats. AD reduced Jv similarly, suggesting that A1-ARs are activated by local production of adenosine. Expression of A1-AR mRNA and protein was higher ( P < 0.01) in microdissected PTs in LS rats compared with NS and HS. We conclude that A1-ARs in the PT are increased by low salt intake and that A1-AR participates in the increased PT reabsorption of solute and fluid in response to low salt intake.

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