Endogenous renal dopamine production regulates phosphate excretion

1994 ◽  
Vol 266 (6) ◽  
pp. F858-F867 ◽  
Author(s):  
A. Debska-Slizien ◽  
P. Ho ◽  
R. Drangova ◽  
A. D. Baines
Keyword(s):  
Brush Border Membrane ◽  
Membrane Vesicle ◽  
Basolateral Membrane ◽  
High Salt Diet ◽  
Salt Diet ◽  
Endogenous Dopamine ◽  
Low Salt ◽  
32P Uptake ◽  
22Na Uptake ◽  
Renal Dopamine

We examined the effect of endogenous dopamine production on Pi and citrate excretion by Wistar rats. Carbidopa (20-40 mumol/kg ip) decreased dopamine, Pi, and citrate excretion within 20 min (86%, 47%, and 38%, respectively); Pi reabsorption increased 11 +/- 4% (P = 0.03). The decreases were sustained for at least 18 h. 3-Hydroxybenzylhydrazine (45 mumol/kg ip) reduced Pi excretion 24%. Benserazide (40 mumol/kg ip and 0.1 mumol/min iv) reduced dopamine excretion (94%) and blocked the effect of carbidopa on Pi and citrate excretion. In isolated perfused kidneys benserazide, carbidopa, and 3-hydroxybenzylhydrazine all decreased Pi excretion. Dopamine (1 mumol/l) added to cortical minceates reduced brush-border membrane vesicle (BBMV) 32P uptake by 8% (P < 0.02) and amiloride-inhibitable 22Na uptake by 19%. Carbidopa added to minceates increased 32P uptake by 12%. Carbidopa pretreatment increased (75%) amiloride-sensitive 22Na uptake into BBMV of rats fed a high-salt diet. Uptake was not increased into BBMV from rats fed a low-salt diet. Carbidopa increased (17%) basolateral membrane Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) gradually over 4 h. Na(+)-K(+)-ATPase did not increase in rats fed a low-phosphorous diet, but did increase when dopa was added to the diet. Thus endogenous dopamine appears to directly control Na(+)-Pi and Na+/H+ transport and secondarily alter basolateral membrane Na(+)-K(+)-ATPase.

Proximal tubular dopamine production regulates basolateral Na-K-ATPase

1992 ◽  
Vol 262 (4) ◽  
pp. F566-F571 ◽  
Author(s):  
A. D. Baines ◽  
P. Ho ◽  
R. Drangova
Keyword(s):  
Brush Border ◽  
Brush Border Membrane ◽  
Sch 23390 ◽  
Basolateral Membrane ◽  
Sodium Dodecyl ◽  
Maximal Activity ◽  
Western Blots ◽  
Salt Diet ◽  
Low Salt ◽  
Proximal Tubular

Regulation of proximal tubular Na-K-adenosine-triphosphatase (ATPase), brush-border membrane Na(+)-H+ antiporter and Na(+)-Pi symporter activity by endogenously produced dopamine was examined in Wistar rats. Na-K-ATPase was measured in basolateral membrane (BLM) fractions permeabilized with alamethicin or sodium dodecyl sulfate (SDS). Carbidopa (5 mg/kg) injected 18 h before removal of kidneys increased maximal activity (Vmax) noncompetitively in cortical BLM but not in other membrane fractions or outer medullary BLM (-2 +/- 4%). Chronic renal denervation did not alter the response. Carbidopa stimulated Na-K-ATPase in cortical BLM from rats eating a normal salt diet with and without 1% saline to drink (+18 +/- 4% and +22 +/- 4%, respectively; P greater than 0.001). Carbidopa did not increase Vmax of BLM Na-K-ATPase from rats eating a low-salt diet (+1.5 +/- 4%); however, when the low-salt diet was supplemented with 1 mM dihydroxyphenylalanine (dopa) to drink for 1 day carbidopa, increased Vmax by 18 +/- 3% (P = 0.018). Carbidopa did not alter the Michaelis constant (Km) for Na or K or inhibitory constant (Ki) for ouabain. Injection of the DA1 antagonist Sch 23390 (2 mg/kg) also increased Na-K-ATPase (18 +/- 4%; P = 0.014). Western blots using a monoclonal alpha-subunit antibody revealed a 22 +/- 8% increase following carbidopa treatment (P = 0.033; n = 19 pairs). Carbidopa had no effect on Na(+)-H+ antiporter activity (22Na uptake) or on Na(+)-32Pi cotransport in brush-border membrane vesicles. These results indicate that dopamine produced in proximal tubules tonically reduces Na-K-ATPase Vmax by decreasing the number of alpha-subunits associated with the BLM.

scholarly journals Urea and NaCl regulate UT-A1 urea transporter in opposing directions via TonEBP pathway during osmotic diuresis

2009 ◽  
Vol 296 (1) ◽  
pp. F67-F77 ◽  
Author(s):  
Yu-Mi Kim ◽  
Wan-Young Kim ◽  
Hyun-Wook Lee ◽  
Jin Kim ◽  
H. Moo Kwon ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Plasma Osmolality ◽  
Urea Concentration ◽  
Urea Transporter ◽  
Osmotic Diuresis ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Protein ◽  
Low Salt ◽  
Urine Concentrating Ability

In our previous studies of varying osmotic diuresis, UT-A1 urea transporter increased when urine and inner medullary (IM) interstitial urea concentration decreased. The purposes of this study were to examine 1) whether IM interstitial tonicity changes with different urine urea concentrations during osmotic dieresis and 2) whether the same result occurs even if the total urinary solute is decreased. Rats were fed a 4% high-salt diet (HSD) or a 5% high-urea diet (HUD) for 2 wk and compared with the control rats fed a regular diet containing 1% NaCl. The urine urea concentration decreased in HSD but increased in HUD. In the IM, UT-A1 and UT-A3 urea transporters, CLC-K1 chloride channel, and tonicity-enhanced binding protein (TonEBP) transcription factor were all increased in HSD and decreased in HUD. Next, rats were fed an 8% low-protein diet (LPD) or a 0.4% low-salt diet (LSD) to decrease the total urinary solute. Urine urea concentration significantly decreased in LPD but significantly increased in LSD. Rats fed the LPD had increased UT-A1 and UT-A3 in the IM base but decreased in the IM tip, resulting in impaired urine concentrating ability. The LSD rats had decreased UT-A1 and UT-A3 in both portions of the IM. CLC-K1 and TonEBP were unchanged by LPD or LSD. We conclude that changes in CLC-K1, UT-A1, UT-A3, and TonEBP play important roles in the renal response to osmotic diuresis in an attempt to minimize changes in plasma osmolality and maintain water homeostasis.

scholarly journals Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase

2012 ◽  
Vol 13 (3) ◽  
pp. 353-359 ◽  
Author(s):  
MA Bayorh ◽  
A Rollins-Hairston ◽  
J Adiyiah ◽  
D Lyn ◽  
D Eatman
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Prostaglandin E ◽  
Renal Tubules ◽  
Protective Effects ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Salt Intake ◽  
Low Salt ◽  
Cox 2

Introduction: The upregulation of cyclooxygenase (COX) expression by aldosterone (ALDO) or high salt diet intake is very interesting and complex in the light of what is known about the role of COX in renal function. Thus, in this study, we hypothesize that apocynin (APC) and/or eplerenone (EPL) inhibit ALDO/salt-induced kidney damage by preventing the production of prostaglandin E2 (PGE2). Methods: Dahl salt-sensitive rats on either a low-salt or high-salt diet were treated with ALDO (0.2 mg pellet) in the presence of EPL (100 mg/kg/day) or APC (1.5 mM). Indirect blood pressure, prostaglandins and ALDO levels and histological changes were measured. Results: Cyclooxygenase-2 (COX-2) levels were upregulated in the renal tubules and peritubular vessels after high-salt intake, and APC attenuated renal tubular COX-2 protein expression induced by ALDO. Plasma PGE2 levels were significantly reduced by ALDO in the rats fed a low-salt diet when compared to rats fed a high-salt diet. PGE2 was blocked by EPL but increased in the presence of APC. Conclusions: The beneficial effects of EPL may be associated with an inhibition of PGE2. The mechanism underlying the protective effects of EPL is clearly distinct from that of APC and suggests that these agents can have differential roles in cardiovascular disease.

Renal arteriolar Na+/Ca2+exchange in salt-sensitive hypertension

1999 ◽  
Vol 276 (4) ◽  
pp. F567-F573 ◽  
Author(s):  
Lawrence D. Nelson ◽  
M. Tino Unlap ◽  
James L. Lewis ◽  
P. Darwin Bell
Keyword(s):  
Cytosolic Calcium ◽  
Ringer Solution ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Vascular Segment ◽  
Low Salt ◽  
Afferent Arterioles ◽  
Salt Sensitive Hypertension ◽  
Exchange Activity

The present studies were performed to assess Na+/Ca2+exchange activity in afferent and efferent arterioles from Dahl/Rapp salt-resistant (R) and salt-sensitive (S) rats. Renal arterioles were obtained by microdissection from S and R rats on either a low-salt (0.3% NaCl) or high-salt (8.0% NaCl) diet. On the high-salt diet, S rats become markedly hypertensive. Cytosolic calcium concentration ([Ca2+]i) was measured in fura 2-loaded arterioles bathed in a Ringer solution in which extracellular Na (Nae) was varied from 150 to 2 mM (Na was replaced with N-methyl-d-glucamine). Baseline [Ca2+]iwas similar in afferent arterioles of R and S rats fed low- and high-salt diet. The change in [Ca2+]i(Δ[Ca2+]i) during reduction in Nae from 150 to 2 mM was 80 ± 10 and 61 ± 3 nM (not significant) in afferent arterioles from R rats fed the low- and high-salt diet, respectively. In afferent arterioles from S rats on a high-salt diet, Δ[Ca2+]iduring reductions in Nae from 150 to 2 mM was attenuated (39 ± 4 nM) relative to the Δ[Ca2+]iof 79 ± 13 nM ( P < 0.05) obtained in afferent arterioles from S rats on a low-salt diet. In efferent arterioles, baseline [Ca2+]iwas similar in R and S rats fed low- and high-salt diets, and Δ[Ca2+]iin response to reduction in Naewas also not different in efferent arterioles from R and S rats fed low- or high-salt diets. Differences in regulation of the exchanger in afferent arterioles of S and R rats were assessed by determining the effects of protein kinase C (PKC) activation by phorbol 12-myristate 13-acetate (PMA, 100 nM) on Δ[Ca2+]iin response to reductions in Naefrom 150 to 2 mM. PMA increased Δ[Ca2+]iin afferent arterioles from R rats but not from S rats. These results suggest that Na+/Ca2+exchange activity is suppressed in afferent arterioles of S rats that are on a high-salt diet. In addition, there appears to be a defect in the PKC-Na+/Ca2+exchange pathway that might contribute to altered [Ca2+]iregulation in this important renal vascular segment in salt-sensitive hypertension.

Salt intake and insulin sensitivity in healthy human volunteers

2007 ◽  
Vol 113 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Raymond R. Townsend ◽  
Shiv Kapoor ◽  
Christopher B. McFadden
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Infusion ◽  
Salt Intake ◽  
Sodium Intake ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Euglycaemic Clamp ◽  
Noradrenaline Concentration ◽  
Low Salt

The literature on salt intake and insulin sensitivity presents a mixed picture, as some studies have shown an increase, whereas others have shown a decrease, in insulin action as sodium intake is enhanced. In some cases, this may relate to the study of salt intake in patients with co-morbidities such as hypertension or diabetes. In the present study, we selected healthy normotensive lean volunteers who underwent a euglycaemic clamp following 6 days of a low-salt diet (20 mmol sodium daily) and, subsequently, 6 days of a high-salt diet (200 mmol sodium daily). Our results show an increase in insulin-mediated glucose disposal during euglycaemic clamp conditions that was significantly higher following the high-salt diet compared with the low-salt diet (7.41±0.41 compared with 6.11±0.40 mg·kg−1 of body weight·min−1 respectively; P=0.03). We measured calf blood flow before and during insulin infusion (no significant change after the two dietary salt interventions was detected) and plasma non-esterified fatty acids (also no significant differences were detected). We observed the expected increases in renin concentration and aldosterone activity in subjects on the low-salt diet, and also observed a significantly less increase in plasma noradrenaline concentration during euglycaemic insulin infusion following the high-salt compared with the low-salt diet. We propose that the 4–5-fold increase in serum aldosterone and the greater increase in plasma noradrenaline concentration following the low-salt intervention compared with the high-salt period may have contributed to the differences in insulin sensitivity following the adjustment in dietary sodium intake.

Guanylyl cyclase/natriuretic peptide receptor-A gene disruption causes increased adrenal angiotensin II and aldosterone levels

2007 ◽  
Vol 293 (1) ◽  
pp. F121-F127 ◽  
Author(s):  
Di Zhao ◽  
Elangovan Vellaichamy ◽  
Naveen K. Somanna ◽  
Kailash N. Pandey
Keyword(s):  
Dependent Manner ◽  
Natriuretic Peptide Receptor ◽  
Ang Ii ◽  
High Salt Diet ◽  
Salt Diet ◽  
Peptide Receptor ◽  
Arterial Blood ◽  
Low Salt ◽  
Natriuretic Peptide Receptor A ◽  
Dose Dependent

Disruption of the guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) gene leads to elevated arterial blood pressure and congestive heart failure in mice lacking NPRA. This study was aimed at determining whether Npr1 (coding for GC-A/NPRA) gene copy number affects adrenal ANG II and aldosterone (Aldo) levels in a gene-dose-dependent manner in Npr1 gene-targeted mice. Adrenal ANG II and Aldo levels increased in 1-copy mice compared with 2-copy mice, but decreased in 3-copy and 4-copy mice. In contrast, renal ANG II levels decreased in 1-copy (25%), 3-copy (38%), and 4-copy (39%) mice compared with 2-copy mice. The low-salt diet stimulated adrenal ANG II and Aldo levels in 1-copy (20 and 2,441%), 2-copy (15 and 2,339%), 3-copy (20 and 424%), and 4-copy (31 and 486%) mice, respectively. The high-salt diet suppressed adrenal ANG II and Aldo levels in 1-copy (46 and 29%) and 2-copy (38 and 17%) mice. On the other hand, the low-salt diet stimulated renal ANG II levels in 1-copy (45%), 2-copy (45%), 3-copy (59%), and 4-copy (48%) mice. However, the high-salt diet suppressed renal ANG II levels in 1-copy (28%) and 2-copy (27%) mice. In conclusion, NPRA signaling antagonizes adrenal ANG II and Aldo levels in a gene-dose dependent manner. Increased adrenal ANG II and Aldo levels may play an important role in elevated arterial blood pressure and progressive hypertension, leading to renal and vascular injury in Npr1 gene-disrupted mice.

Effect of Salt Intake and Potassium Supplementation on Urinary Renalase and Serum Dopamine Levels in Chinese Adults

Cardiology ◽  
2015 ◽  
Vol 130 (4) ◽  
pp. 242-248 ◽  
Author(s):  
Yang Wang ◽  
Dan Wang ◽  
Chao Chu ◽  
Jian-Jun Mu ◽  
Man Wang ◽  
...  
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
High Potassium ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Potassium Intake ◽  
Potassium Supplementation ◽  
Low Salt

Objective: The aim of our study was to assess the effects of altered salt and potassium intake on urinary renalase and serum dopamine levels in humans. Methods: Forty-two subjects (28-65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for an additional 7 days (18.0 g/day of NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). Results: Urinary renalase excretions were significantly higher during the high-salt diet intervention than during the low-salt diet. During high-potassium intake, urinary renalase excretions were not significantly different from the high-salt diet, whereas they were significantly higher than the low-salt levels. Serum dopamine levels exhibited similar trends across the interventions. Additionally, a significant positive relationship was observed between the urine renalase and serum dopamine among the different dietary interventions. Also, 24-hour urinary sodium excretion positively correlated with urine renalase and serum dopamine in the whole population. Conclusions: The present study indicates that dietary salt intake and potassium supplementation increase urinary renalase and serum dopamine levels in Chinese subjects.

scholarly journals Tubuloglomerular feedback in Dahl rats

1998 ◽  
Vol 274 (6) ◽  
pp. R1561-R1569 ◽  
Author(s):  
Finn M. Karlsen ◽  
Paul P. Leyssac ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Flow Rate ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Compensatory Response ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sprague Dawley Rats ◽  
Intratubular Pressure ◽  
Low Salt ◽  
Experimental Rat Model

We have previously demonstrated a loss of autoregulation in Dahl salt-sensitive (Dahl-S) rats rendered hypertensive on a high-salt diet. To determine whether this was due to a decreased activity of either the myogenic or the tubuloglomerular feedback (TGF) response, we tested the TGF response in both Dahl-S and salt-resistant Dahl rats on high- and low-salt diets. TGF was investigated in the closed-loop mode with a videometric technique, in which the response in late proximal flow rate to perturbations in Henle flow rate was measured. All Dahl rats showed a similar compensatory response to perturbations around the natural operating point, with a TGF response that was more efficient than in normotensive Sprague-Dawley rats. No evidence of decreased TGF responsiveness in hypertensive Dahl-S rats was found. The results suggest that the loss of autoregulation in hypertensive Dahl-S rats is due to a compromised myogenic response. We also measured the free-flow proximal intratubular pressure in Dahl rats. Perfectly regular oscillations were demonstrated in all Dahl series, including the hypertensive Dahl-S rats. This is the first demonstration of regular oscillations in an experimental rat model of hypertension.

Renal endosomes contain angiotensin peptides, converting enzyme, and AT1A receptors

1999 ◽  
Vol 277 (2) ◽  
pp. F303-F311 ◽  
Author(s):  
John D. Imig ◽  
Gabriel L. Navar ◽  
Li-Xian Zou ◽  
Katie C. O’Reilly ◽  
Patricia L. Allen ◽  
...  
Keyword(s):  
High Salt ◽  
Dietary Sodium ◽  
Kidney Cortex ◽  
Ang Ii ◽  
Converting Enzyme ◽  
High Salt Diet ◽  
Salt Diet ◽  
Angiotensin Peptides ◽  
Low Salt ◽  
Ace Activity

Kidney cortex and proximal tubular angiotensin II (ANG II) levels are greater than can be explained on the basis of circulating ANG II, suggesting intrarenal compartmentalization of these peptides. One possible site of intracellular accumulation is the endosomes. In the present study, we tested for endosomal ANG I, ANG II, angiotensin type 1A receptor (AT1A), and angiotensin converting enzyme (ACE) activity and determined whether these levels are regulated by salt intake. Male Sprague-Dawley rats were fed chow containing either high or low dietary sodium for 10–14 days. Blood and kidneys were harvested and processed for measurement of plasma, kidney, and renal intermicrovillar cleft and endosomal angiotensin levels. Kidney ANG I averaged 179 ± 20 fmol/g and ANG II averaged 258 ± 36 fmol/g in rats fed a high-sodium diet and were significantly higher, averaging 347 ± 58 fmol/g and 386 ± 55 fmol/g, respectively, in rats fed a low-salt diet. Renal intermicrovillar clefts and endosomes contained ANG I and ANG II. Intermicrovillar cleft ANG I and ANG II levels averaged 8.4 ± 2.6 and 74 ± 26 fmol/mg, respectively, in rats fed a high-salt diet and 7.6 ± 1.7 and 70 ± 25 fmol/mg in rats fed a low-salt diet. Endosomal ANG I and ANG II levels averaged 12.3 ± 4.4 and 43 ± 19 fmol/mg, respectively, in rats fed a high-salt diet, and these levels were similar to those observed in rats fed a low-salt diet. Renal endosomes from rats fed a low-salt diet demonstrated significantly more AT1A receptor binding compared with rats fed a high-salt diet. ACE activity was detectable in renal intermicrovillar clefts and was 2.5-fold higher than the levels observed in renal endosomes. Acute enalaprilat treatment decreased ACE activity in renal intermicrovillar clefts by 90% and in renal endosomes by 84%. Likewise, intermicrovillar cleft and endosomal ANG II levels decreased by 61% and 52%, respectively, in enalaprilat-treated animals. These data demonstrate the presence of intact angiotensin peptides and ACE activity in renal intermicrovillar clefts and endosomes, indicating that intact angiotensin peptides are formed and/or trafficked through intracellular endosomal compartments and are dependent on ACE activity.

scholarly journals Microvascular flow and tissue Po 2 in skeletal muscle of chronic reduced renal mass hypertensive rats

2000 ◽  
Vol 279 (5) ◽  
pp. H2295-H2302 ◽  
Author(s):  
Julian H. Lombard ◽  
Jefferson C. Frisbee ◽  
Andrew S. Greene ◽  
Antal G. Hudetz ◽  
Richard J. Roman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Chronic Exposure ◽  
Renal Mass ◽  
Tissue Oxygenation ◽  
Hypertensive Rats ◽  
Third Order ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Salt ◽  
Flow Capillary

This study determined whether arteriolar blood flow, capillary red blood cell (RBC) velocity, capillary hematocrit (Hctcap), and tissue Po 2 are altered in cremaster muscles of rats with chronic reduced renal mass hypertension (RRM-HT) relative to normotensive rats on high- or low-salt (NT-HS vs. NT-LS) diet. The blood flow in first- through third-order arterioles was not different between NT and HT rats, either at rest or during maximal relaxation of the vessels with 10−4 M adenosine. Capillary RBC velocity was similar between the groups at rest but was elevated in RRM-HT and NT-HS rats during adenosine superfusion. Hctcap was reduced at rest in RRM-HT and NT-HS rats compared with NT-LS and was reduced in RRM-HT rats during adenosine-induced dilation. Tissue Po 2 was reduced in RRM-HT and NT-HS rats compared with NT-LS rats during control conditions and was lower in RRM-HT than in NT-LS rats during adenosine-induced dilation. These results indicate that both RRM-HT and chronic exposure of normotensive rats to a high-salt diet lead to reduced tissue oxygenation, despite the maintenance of normal arteriolar blood flow.

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