scholarly journals Dietary salt induces transcription of the prostaglandin transporter gene in renal collecting ducts

2008 ◽  
Vol 295 (3) ◽  
pp. F765-F771 ◽  
Author(s):  
Yuling Chi ◽  
Michael L. Pucci ◽  
Victor L. Schuster
Keyword(s):  
Salt Intake ◽  
Collecting Duct ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Dietary Salt ◽  
Water Excretion ◽  
Salt Loading ◽  
Dietary Salt Intake ◽  
High Sodium ◽  
Transgenic Mouse Line

Prostaglandin E2 (PGE2) plays an important role in maintaining body fluid homeostasis by activating its receptors on the renal collecting duct (CD) to stimulate renal Na+ and water excretion. The PG carrier prostaglandin transporter (PGT) is expressed on the CD apical membrane, where it mediates PG reuptake as part of the termination of autocrine PG signaling. Here we tested the hypothesis that dietary salt loading regulates PGT gene transcription in renal CDs. We placed green fluorescence protein (GFP) under control of 3.3 kb of the mouse PGT promoter and injected this construct into the pronuclei of fertilized FVB mouse eggs. Four of thirty-eight offspring were GFP positive by genotyping. We extensively characterized one (no. 29) PGT-GFP transgenic mouse line. On microscopic examination, GFP was expressed in CDs as determined by their expression of aquaporin-2. We fed mice a low (0.03% NaCl)-, normal (0.3% NaCl)-, or high-salt (3% NaCl) diet for 2 wk and quantified CD GFP expression. The average number of GFP-positive CD cells per microscopic section varied directly with dietary salt intake. Compared with mice on the control (0.3% sodium) diet, mice on a low-sodium (0.03%) diet had reduced numbers of GFP-positive cells (71% of control, P < 0.001), whereas mice on a high-sodium (3%) diet had increased numbers of GFP-positive cells (139% of control, P < 0.001). This increase in apparent CD PGT transcription resulted in a 51–55% increase ( P < 0.001) in whole kidney PGT mRNA levels as determined by real-time PCR. The regulation of PG signal termination via reuptake represents a new pathway for controlling renal Na+ balance.

Abstract 42: AT1 Angiotensin Receptors in Principal Cells of the Collecting Duct Have Minimal Impact on Blood Pressure and the Development of Hypertension.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Daian Chen ◽  
Johannes Stegbauer ◽  
Matthew A. Sparks ◽  
Donald Kohan ◽  
Susan B. Gurley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Collecting Duct ◽  
Weight Ratio ◽  
Angiotensin Receptors ◽  
Mrna Levels ◽  
Ang Ii ◽  
Mouse Line ◽  
Dietary Salt ◽  
Transgenic Mouse Line

The main actions of the renin angiotensin system to control blood pressure (BP) are mediated by the angiotensin type 1 receptors (AT 1 R). The major murine AT 1 R isoform, AT 1A is highly expressed in epithelial cells throughout the nephron, including the collecting duct (CD). The CD consists of two cell types, principal (PC) and intercalated cells (IC) with distinct functions. Activation of AT 1 R in PC stimulates solute reabsorption in the CD by increasing the activity of epithelial sodium channels. To examine the role of the AT 1A R in the PC to BP regulation and the development of hypertension in vivo , we generated inbred 129SvEv mice with cell-specific deletion of AT 1A R in PC (PC-KO, n=6). AQP2-Cre transgenic mouse line was used to excise the floxed Agtr1a allele in PC. mTmG reporter mouse line was used to confirm specific expression of AQP2-Cre transgene in PC, and found the pattern of expression to be predominantly in medullary CD. Using RT-PCR, mRNA levels for AT 1A R were reduced by ≈50% in the inner medulla of PC-KO mice ( P <0.05), but unaffected in cortex. Baseline BP measured by radiotelemetry was similar between PC-KO (122±1.6 mm Hg) and controls (122±1.6 mm Hg). During one week of feeding a low salt (<0.002% NaCl) diet, MAP fell significantly (P<0.05) and to a similar extent in both groups, (PC-KO: 116±1 mm Hg; Controls: 117±2 mm Hg). High salt (6% NaCl) diet increased BP (P<0.01), but was not different between groups (PC-KO: 129±2 mm Hg; Controls: 131±2 mm Hg). Finally, we induced hypertension with chronic infusion of Ang II (1000 ng/kg/min) by osmotic mini-pumps. During the initial phase (days 1-8), there was a modest but significant attenuation of hypertension in PC-KO (167±7 mm Hg) compared to controls (178±3 mm Hg, P<0.001). However, by day 9 levels of BP were indistinguishable between groups and there was no difference in BP in the later phase (days 9-14) of hypertension (PC-KO: 175±12 mm Hg; Controls: 177±7 mm Hg). Heart to body weight ratio after Ang II infusion was not different between groups. In summary, AT 1A R in PC of the medullary CD have little influence on BP, adaptation to changes in dietary salt intake or development of hypertension. We suggest that other mediators, such as aldosterone, may have a more important role to influence sodium handling in this nephron segment.

Role of prostaglandins in collecting duct-derived endothelin-1 regulation of blood pressure and water excretion

2007 ◽  
Vol 293 (6) ◽  
pp. F1805-F1810 ◽  
Author(s):  
Yuqiang Ge ◽  
Kevin A. Strait ◽  
Peter K. Stricklett ◽  
Tianxin Yang ◽  
Donald E. Kohan
Keyword(s):  
Blood Pressure ◽  
Collecting Duct ◽  
Urine Volume ◽  
Mrna Levels ◽  
Water Excretion ◽  
Salt Loading ◽  
Endothelin 1 ◽  
Cox 2 ◽  
Cox 1

Collecting duct (CD)-derived endothelin-1 (ET-1) exerts natriuretic, diuretic, and hypotensive effects. In vitro studies have implicated cyclooxygenase (COX) metabolites, and particularly PGE2, as important mediators of CD ET-1 effects. However, it is unknown whether PGE2 mediates CD-derived ET-1 actions in vivo. To test this, CD ET-1 knockout (KO) and control mice were studied. During normal salt and water intake, urinary PGE2 excretion was unexpectedly increased in CD ET-1 KO mice compared with controls. Salt loading markedly increased urinary PGE2 excretion in both groups of mice; however, the levels remained relatively higher in KO animals. Acutely isolated inner medullary collecting duct (IMCD) from KO mice also had increased PGE2 production. The increased IMCD PGE2 was COX-2 dependent, since NS-398 blocked all PGE2 production. However, increased CD ET-1 KO COX-2 protein or mRNA could not be detected in inner medulla or IMCD, respectively. Inner medullary COX-1 mRNA and protein levels and IMCD COX-1 mRNA levels were unaffected by Na intake or CD ET-1 KO. KO mice on a normal or high-Na diet had elevated blood pressure compared with controls; this difference was not altered by indomethacin or NS-398 treatment. However, indomethacin or NS-398 did increase urine osmolality and reduce urine volume in KO, but not control, animals. In summary, IMCD COX-2-dependent PGE2 production is increased in CD ET-1 KO mice, indicating that CD-derived ET-1 is not a primary regulator of IMCD PGE2. Furthermore, the increased PGE2 in CD ET-1 KO mice partly compensates for loss of ET-1 with respect to maintaining urinary water excretion, but not in blood pressure control.

Regulation of cyclooxygenase expression in the kidney by dietary salt intake

1998 ◽  
Vol 274 (3) ◽  
pp. F481-F489 ◽  
Author(s):  
Tianxin Yang ◽  
Inderjit Singh ◽  
Hang Pham ◽  
Daqing Sun ◽  
Ann Smart ◽  
...  
Keyword(s):  
Salt Intake ◽  
Collecting Duct ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Protein Levels ◽  
Low Salt ◽  
Cox 2 ◽  
Cox 1

The present studies were undertaken to determine the effect of dietary salt intake on the renal expression of cyclooxygenase-1 (COX-1) and -2 (COX-2). Protein levels were assessed by Western blotting, and mRNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) on cDNA prepared from kidney regions, dissected nephron segments, and cultured renal cells. Both isoforms were expressed at high levels in inner medulla (IM), with low levels detected in outer medulla and cortex. COX-1 mRNA was present in the glomerulus and all along the collecting duct, whereas COX-2 mRNA was restricted to the macula densa-containing segment (MD), cortical thick ascending limb (CTAL), and, at significantly lower levels, in the inner medullary collecting duct. Both isoforms were highly expressed at high levels in cultured medullary interstitial cells and at lower levels in primary mesangial cells and collecting duct cell lines. Maintaining rats on a low- or high-NaCl diet for 1 wk did not affect expression of COX-1. In IM of rats treated with a high-salt diet, COX-2 mRNA increased 4.5-fold, and protein levels increased 9.5-fold. In contrast, cortical COX-2 mRNA levels decreased 2.9-fold in rats on a high-salt diet and increased 3.3-fold in rats on a low-salt diet. A low-salt diet increased COX-2 mRNA 7.7-fold in MD and 3.3-fold in CTAL. Divergent regulation of COX-2 in cortex and medulla by dietary salt suggests that prostaglandins in different kidney regions serve different functions, with medullary production playing a role in promoting the excretion of salt and water in volume overload, whereas cortical prostaglandins may protect glomerular circulation in volume depletion.

Immunoreactive Substance P in Human Plasma: Response to Changes in Posture and Sodium Balance

1980 ◽  
Vol 59 (1) ◽  
pp. 75-77 ◽  
Author(s):  
H. J. Kramer ◽  
R. Düsing ◽  
H. Stelkens ◽  
R. Heinrich ◽  
J. Kipnowski ◽  
...  
Keyword(s):  
Substance P ◽  
Salt Intake ◽  
Sodium Intake ◽  
Plasma Concentrations ◽  
Mean Value ◽  
Dietary Sodium ◽  
Sodium Balance ◽  
Dietary Salt ◽  
Dietary Salt Intake ◽  
High Sodium

1. In healthy volunteers plasma concentrations of immunoreactive substance P were measured in response to changes in posture and dietary salt intake. 2. In 14 subjects plasma immunoreactive substance P was 168 ± 31 pmol/l when subjects were supine and 401 ± 51 pmol/l (P < 0.001) when they were ambulant. 3. Measurement of supine plasma immunoreactive substance P at 6 h intervals gave a mean value of 240 ± 39 pmol/l at 14.00 hours and a lowest value of 76 ± 9 pmol/l at 02.00 hours. 4. In eight healthy subjects plasma immunoreactive substance P rose only slightly from 169 ± 41 pmol/l, on a sodium intake ad lib., to 244 ± 45 pmol/l by day 4 of dietary sodium restriction (35 mmol/day) and significantly fell to 51 ± 20 pmol/l (P < 0.001) by day 4 of high sodium intake (350 mmol/day). 5. Although exogenous substance P was shown to be natriuretic in dog and rat, the present results do not favour a role of endogenous substance P as a circulating natriuretic factor in man.

Clearance of endogenous lithium in humans: altered dietary salt intake and comparison with exogenous lithium clearance

1995 ◽  
Vol 268 (4) ◽  
pp. F718-F722 ◽  
Author(s):  
E. Folkerd ◽  
D. R. Singer ◽  
F. P. Cappuccio ◽  
N. D. Markandu ◽  
B. Sampson ◽  
...  
Keyword(s):  
Salt Intake ◽  
Sodium Intake ◽  
Lithium Concentration ◽  
Fractional Excretion ◽  
Dietary Sodium ◽  
Lithium Clearance ◽  
Dietary Salt ◽  
Renal Handling ◽  
Dietary Salt Intake ◽  
High Sodium

We compared endogenous with exogenous lithium clearance (CLi) and studied the effects of dietary salt intake on endogenous CLi in healthy volunteers. Lithium was detectable within a narrow fourfold range in serum and in urine in all 25 subjects studied [serum (n = 25), mean 0.27 +/- 0.02 mumol/l, range 0.13-0.55 mumol/l; urine (n = 20), range 1.49–7.32, mean 4.09 +/- 0.36 mumol/24 h]. Mean clearance and fractional excretion of endogenous lithium were lower (15.2 +/- 2.0 ml/min and 16.4 +/- 2.1%, respectively) compared with results obtained using the exogenous CLi technique (25.5 +/- 1.7 ml/min and 27.9 +/- 2.1%; P < 0.01 and P < 0.05, respectively; n = 17). In a separate group of six normal subjects, absolute (8.7 +/- 2.9 vs. 20.7 +/- 3.8 ml/min) and fractional excretion of lithium (8.3 +/- 2.9 vs. 18.0 +/- 5.1%) were significantly lower on 5 days of low (31 +/- 10 mmol/day) vs. high sodium intake (357 +/- 78 mmol/day; P < 0.05). Use of endogenous CLi precludes the need for lithium tablets. This could be a particular advantage in population studies and permits serial measurement of CLi on different days. Our results show that it is important to take dietary sodium intake into account in studies of endogenous CLi. Lower values for endogenous compared with exogenous CLi could reflect differences in renal handling depending on the plasma lithium concentration. This clearly requires further study.

Arterial baroreceptor denervation impairs long-term regulation of arterial pressure during dietary salt loading

1998 ◽  
Vol 275 (5) ◽  
pp. H1558-H1566 ◽  
Author(s):  
John W. Osborn ◽  
Barbara J. Hornfeldt
Keyword(s):  
Arterial Pressure ◽  
Salt Intake ◽  
Critical Role ◽  
Dietary Salt ◽  
Dark Cycle ◽  
Salt Loading ◽  
Dietary Salt Intake ◽  
The Third ◽  
Arterial Baroreceptors

Experiments were performed to examine the contribution of arterial baroreceptors to long-term regulation of mean arterial pressure (MAP) during changes in dietary salt intake. Normotensive Sprague-Dawley rats were subjected to either sinoaortic denervation (SAD; n= 8) or Sham surgery ( n = 6) and instrumented 1 wk later with radiotelemetry transmitters for continuous minute-to-minute monitoring of MAP and heart rate (HR) over the 8-wk protocol. Rats consumed three levels of dietary NaCl: 0.4% NaCl ( week 1), 4.0% NaCl ( weeks 2–4), and 8.0% NaCl ( weeks 5–7). Rats returned to a 0.4% NaCl diet during the eighth week of the experiment. During week 1 (0.4% NaCl), there were no differences between Sham and SAD groups for 24-h averages of MAP or HR. However, by the third week of 4.0% NaCl, 24-h MAP was elevated significantly from baseline in SAD (10 ± 2 mmHg) but not Sham (1 ± 1 mmHg) rats. By the end of the third week of 8.0% NaCl diet, 24-h MAP was elevated 15 ± 2 mmHg above control in SAD rats compared with a 4 ± 1 mmHg increase in Sham rats ( P < 0.05). Hourly analysis of the final 72 h of each level of dietary salt revealed a marked effect of dietary NaCl on MAP in SAD rats, particularly during the dark cycle. MAP increased ∼20 and 30 mmHg in SAD rats over the 12-h dark cycle for 4.0 and 8.0% NaCl diets, respectively. In contrast, increased dietary NaCl had no effect on MAP during any phase of the light or dark period in Sham rats. These data support the hypothesis that arterial baroreceptors play a critical role in long-term regulation of MAP under conditions of altered dietary salt intake. Finally, hourly analysis of MAP revealed that the majority of the hypertensive response to increased NaCl occurs during the dark cycle in SAD rats. Hence, previous investigations may have underestimated the magnitude of the hypertensive response to increased dietary NaCl in animals with baroreceptor dysfunction.

Urinary excretion of dihydroxyphenylalanine and dopamine during alterations of dietary salt intake in humans

1989 ◽  
Vol 76 (5) ◽  
pp. 517-522 ◽  
Author(s):  
David S. Goldstein ◽  
Robin Stull ◽  
Graeme Eisenhofer ◽  
John R. Gill
Keyword(s):  
Urinary Excretion ◽  
Salt Intake ◽  
Sodium Intake ◽  
Sodium Balance ◽  
Dietary Salt ◽  
Proximal Tubular Cells ◽  
Salt Loading ◽  
Dietary Salt Intake ◽  
Tubular Cells ◽  
Proximal Tubular

1. Urinary excretion of dopamine (DA) increases during dietary salt loading. The majority of urinary DA is derived from circulating dihydroxyphenylalanine (dopa). Whether the increase in urinary DA excretion during salt loading results from increased efficiency of uptake of dopa by proximal tubular cells of the kidney, facilitation of intracellular conversion of dopa to DA, or increased delivery of dopa to tubular uptake sites, has been unknown. 2. In 10 inpatient normal volunteers on a constant diet, daily excretion of dopa and DA was assessed during normal sodium intake (109 mmol/day) for 1 week, low sodium intake (9 mmol/day) for 1 week and high sodium intake (249 mmol/day) for 1 week. 3. Urinary DA excretion exceeded urinary dopa excretion by about tenfold, and the excretion of both DA and dopa increased by about twofold between the low and high salt diets, with similar proportionate changes. Plasma dopa was unchanged by dietary salt manipulation. 4. The results indicate that increases in urinary DA excretion during dietary salt loading can be accounted for by increased delivery of dopa to sites of uptake by proximal tubular cells. Since dopa is released into the bloodstream by sympathetic nerve endings and by the brain, and since interference with decarboxylation of dopa attenuates natriuretic responses, dopa may function indirectly as a neurohormone involved in homoeostatic regulation of sodium balance.

Effects of changes in dietary sodium intake on aortic sodium pump activity in the rat

1987 ◽  
Vol 72 (1) ◽  
pp. 143-146 ◽  
Author(s):  
Richard Bradlaugh ◽  
Robert F. Bing ◽  
John D. Swales ◽  
Herbert Thurston
Keyword(s):  
Smooth Muscle ◽  
Sodium Pump ◽  
Salt Intake ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Dietary Salt ◽  
Salt Loading ◽  
Sodium Efflux ◽  
Salt Restriction ◽  
Dietary Salt Intake

1. Aortic smooth muscle sodium efflux was studied in normal rats undergoing salt restriction or salt loading. 2. Sodium efflux rate constant was not changed by salt loading but fell significantly with salt restriction. This change was not associated with a fall in blood pressure. 3. These studies show that smooth muscle sodium transport can be influenced by dietary salt intake but do not support the concept that salt loading leads to the inhibition of the vascular smooth muscle sodium pump.

scholarly journals Adenosine inhibits the basolateral Cl− ClC-K2/b channel in collecting duct intercalated cells

2020 ◽  
Vol 318 (4) ◽  
pp. F870-F877
Author(s):  
Oleg Zaika ◽  
Viktor N. Tomilin ◽  
Oleh Pochynyuk
Keyword(s):  
Salt Intake ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Inhibitory Effect ◽  
Intercalated Cells ◽  
Dietary Salt ◽  
Open Probability ◽  
Salt Loading ◽  
Principal Cells ◽  
High Salt Intake

Adenosine plays an important role in various aspects of kidney physiology, but the specific targets and mechanisms of actions are not completely understood. The collecting duct has the highest expression of adenosine receptors, particularly adenosine A1 receptors (A1Rs). Interstitial adenosine levels are greatly increased up to a micromolar range in response to dietary salt loading. We have previously shown that the basolateral membrane of principal cells has primarily K+ conductance mediated by Kir4.1/5.1 channels to mediate K+ recycling and to set up a favorable driving force for Na+/K+ exchange ( 47 ). Intercalated cells express the Cl− ClC-K2/b channel mediating transcellular Cl− reabsorption. Using patch-clamp electrophysiology in freshly isolated mouse collecting ducts, we found that acute application of adenosine reversely inhibits ClC-K2/b open probability from 0.31 ± 0.04 to 0.17 ± 0.06 and to 0.10 ± 0.05 for 1 and 10 µM, respectively. In contrast, adenosine (10 µM) had no measureable effect on Kir4.1/5.1 channel activity in principal cells. The inhibitory effect of adenosine on ClC-K2/b was abolished in the presence of the A1R blocker 8-cyclopentyl-1,3-dipropylxanthine (10 µM). Consistently, application of the A1R agonist N6-cyclohexyladenosine (1 µM) recapitulated the inhibitory action of adenosine on ClC-K2/b open probability. The effects of adenosine signaling in the collecting duct were independent from its purinergic counterpartner, ATP, having no measurable actions on ClC-K2/b and Kir4.1/5.1. Overall, we demonstrated that adenosine selectively inhibits ClC-K2/b activity in intercalated cells by targeting A1Rs. We propose that inhibition of transcellular Cl− reabsorption in the collecting duct by adenosine would aid in augmenting NaCl excretion during high salt intake.

Coordinate regulation of renal expression of nitric oxide synthase, renin, and angiotensinogen mRNA by dietary salt

1996 ◽  
Vol 270 (6) ◽  
pp. F1027-F1037 ◽  
Author(s):  
I. Singh ◽  
M. Grams ◽  
W. H. Wang ◽  
T. Yang ◽  
P. Killen ◽  
...  
Keyword(s):  
Renal Cortex ◽  
Salt Intake ◽  
High Salt ◽  
Mrna Levels ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Low Salt ◽  
Oxide Synthase

Experiments were performed to examine the effect of changes in dietary salt intake on the neuronal form of the constitutive nitric oxide synthase (ncNOS, type I NOS), renin, and angiotensinogen mRNA expression in the kidney. Three groups of Sprague-Dawley rats were studied as follows: rats maintained on a 3% Na diet plus 0.45% NaCl in the drinking fluid for 7 days (high salt), rats given a single injection of furosemide (2 mg/kg i.p.) and a 0.03% Na diet for 7 days (low salt), and rats on a diet containing 0.2% Na (control). mRNA expression was assessed with reverse transcription-polymerase chain reaction (RT-PCR) methods using cDNA prepared from samples of renal cortex and microdissected tubular segments. ncNOS PCR products were quantified by comparison with a dilution series of a mutant deletion template. Compared with their respective control, ncNOS mRNA levels in renal cortical tissue were elevated in rats on a low-salt diet and reduced in rats on a high-salt diet. Similar changes were seen in the expression of renin and angiotensinogen mRNA. Dietary salt intake did not alter the mRNA levels for ncNOS from the inner medulla or for endothelial constitutive NOS (ecNOS, type III NOS) and inducible NOS (iNOS, type II NOS) in the renal cortex. ncNOS mRNA was found in glomeruli dissected with the macula densa-containing segment (MDCS), but only at marginal levels in glomeruli without MDCS. Furthermore, a low-salt diet stimulated ncNOS mRNA in glomeruli with MDCS by 6.2-fold compared with a high-salt diet. There was no effect of salt diet on ncNOS mRNA in glomeruli without MDCS or in inner medullary collecting ducts. These results suggest that ncNOS expression in macula densa cells is inversely regulated by salt intake, thus following the known response of the renin-angiotensin system to changes in salt balance.

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