The control of sodium excretion

The kidneys of a normal man filter approximately 24,000 meq sodium/day, reabsorb about 23,900, and yet can make a 1--2 meq change in 24-h urinary sodium excretion. The control of urinary sodium excretion, therefore, depends, first, on ensuring that the bulk of the sodium is reabsorbed, a function which is carried out in the proximal tubule and ascending loop of Henle. Second, it depends on adjusting the reabsorption of the small quantity of sodium which is delivered into the collecting duct so that the amount excreted in the urine is that required to maintain sodium balance. The bulk reabsorptive mechanisms can be considered as buffers to prevent large fluctuations in the amount of sodium delivered to the collecting duct, thus facilitating the fine adjustments of reabsorption which are made at this site. In conditions other than extreme salt loading or deprivation, changes in sodium reabsorption in the proximal tubule and loop of Henle probably have little, if any, effect on urinary sodium excretion. Sodium reabsorption in the proximal tubule and the collecting duct appears to be influenced by unidentified circulating substances.

Download Full-text

Altered expression of renal aquaporins and Na+ transporters in rats treated with L-type calcium blocker

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.280.6.r1632 ◽

2001 ◽

Vol 280 (6) ◽

pp. R1632-R1641 ◽

Cited By ~ 5

Author(s):

Weidong Wang ◽

Tae-Hwan Kwon ◽

Chunling Li ◽

Allan Flyvbjerg ◽

Mark A. Knepper ◽

...

Keyword(s):

Proximal Tubule ◽

Sodium Excretion ◽

Urine Output ◽

Collecting Duct ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Compensatory Mechanism ◽

Thick Ascending Limb ◽

Water Reabsorption ◽

Altered Expression

Nifedipine, a calcium antagonist, has diuretic and natriuretic properties. However, the molecular mechanisms by which these effects are produced are poorly understood. We examined kidney abundance of aquaporins (AQP1, AQP2, and AQP3) and major sodium transporters [type 3 Na/H exchanger (NHE-3); type 2 Na-Pi cotransporter (NaPi-2); Na-K-ATPase; type 1 bumetanide-sensitive cotransporter (BSC-1); and thiazide-sensitive Na-Cl cotransporter (TSC)] as well as inner medullary abundance of AQP2, phosphorylated-AQP2 (p-AQP2), AQP3, and calcium-sensing receptor (CaR). Rats treated with nifedipine orally (700 mg/kg) for 19 days had a significant increase in urine output, whereas urinary osmolality and solute-free water reabsorption were markedly reduced. Consistent with this, immunoblotting revealed a significant decrease in the abundance of whole kidney AQP2 (47 ± 7% of control rats, P< 0.05) and in inner medullary AQP2 (60 ± 7%) as well as in p-AQP2 abundance (17 ± 6%) in nifedipine-treated rats. In contrast, whole kidney AQP3 abundance was significantly increased (219 ± 28%). Of potential importance in modulating AQP2 levels, the abundance of CaR in the inner medulla was significantly increased (295 ± 25%) in nifedipine-treated rats. Nifedipine treatment was also associated with increased urinary sodium excretion. Consistent with this, semiquantitative immunoblotting revealed significant reductions in the abundance of proximal tubule Na+ transporters: NHE-3 (3 ± 1%), NaPi-2 (53 ± 12%), and Na-K-ATPase (74 ± 5%). In contrast, the abundance of the distal tubule Na-Cl cotransporter (TSC) was markedly increased (240 ± 29%), whereas BSC-1 in the thick ascending limb was not altered. In conclusion, 1) increased urine output and reduced urinary concentration in nifedipine-treated-rats may, in part, be due to downregulation of AQP2 and p-AQP2 levels; 2) CaR might be involved in the regulation of water reabsorption in the inner medulla collecting duct; 3) reduced expression of proximal tubule Na+ transporters (NHE-3, NaPi-2, and Na, K-ATPase) may be involved in the increased urinary sodium excretion; and 4) increase in TSC expression may occur as a compensatory mechanism.

Download Full-text

Proximal tubule response in aldosterone escape

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.1.r86 ◽

1989 ◽

Vol 256 (1) ◽

pp. R86-R90 ◽

Cited By ~ 3

Author(s):

J. M. Gonzalez-Campoy ◽

J. Kachelski ◽

J. C. Burnett ◽

J. C. Romero ◽

J. P. Granger ◽

...

Keyword(s):

Proximal Tubule ◽

Sodium Excretion ◽

Plasma Renin ◽

Fractional Excretion ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Sodium Reabsorption ◽

Hormonal Changes ◽

Proximal Tubular ◽

Temporal Profiles

The response of the proximal tubule to chronic aldosterone administration (15 micrograms.kg-1.day-1) was evaluated in eight conscious female mongrel dogs. Temporal profiles between hemodynamic and hormonal changes and the fractional excretions of sodium and lithium were established. Aldosterone infusion resulted in a significant decrease in urinary sodium excretion from 9.2 +/- 1.3 to 5.8 +/- 0.9 meq/h after 1 day, returning to normal by the 5th day. These changes in urinary sodium excretion were associated with significant elevations of the mean arterial pressure (MAP) from 105 +/- 5 to 111 +/- 6 mmHg and plasma atrial natriuretic factor concentrations (ANF) from 30 +/- 2 to 57 +/- 7 pg/ml beginning the 1st day of infusion. Plasma renin activity (PRA), on the other hand, was depressed by aldosterone, falling below the level of detectability. The fractional excretion of lithium increased significantly by day 2 of aldosterone infusion (from 29 +/- 3 to 44 +/- 6%), reflecting the proximal tubular response to the above changes. We conclude that the proximal tubule responds to increases in MAP and ANF and decreases in PRA during aldosterone infusion by decreasing sodium reabsorption. Subsequent nephron segments must also respond to the volume expansion produced by aldosterone, since the sustained proximal tubule natriuretic response is insufficient to explain all of escape.

Download Full-text

Collecting Duct Is a Site of Sodium Retention in PAN Nephrosis: A Rationale for Amiloride Therapy

Journal of the American Society of Nephrology ◽

10.1681/asn.v123598 ◽

2001 ◽

Vol 12 (3) ◽

pp. 598-601 ◽

Cited By ~ 1

Author(s):

GEORGES DESCHÊNES ◽

MONIKA WITTNER ◽

ANTONIO DI STEFANO ◽

SYLVIE JOUNIER ◽

ALAIN DOUCET

Keyword(s):

Collecting Duct ◽

Urinary Sodium Excretion ◽

Sodium Balance ◽

Sodium Reabsorption ◽

Puromycin Aminonucleoside ◽

Aldosterone Receptor ◽

Collecting Tubules ◽

A Site

Abstract. Micropuncture studies of the distal nephron and measurements of Na,K-ATPase activity in microdissected collecting tubules have suggested that renal retention of sodium in puromycin aminonucleoside (PAN) nephrotic rats originates in the collecting duct. The present study demonstrated this hypothesis by in vitro microperfusion and showed that amiloride was able to restore sodium balance. Indeed, isolated perfused cortical collecting ducts from PAN-treated rats exhibited an abnormally high transepithelial sodium reabsorption that was abolished by amiloride, and in vivo administration of amiloride fully prevented decreased urinary sodium excretion and positive sodium balance in nephrotic rats. As expected from the aldosterone independence of Na+ retention in PAN nephrotic rats, blockade of aldosterone receptor by potassium canrenoate did not alter urinary Na+ excretion, Na+ balance, or ascites formation in PAN nephrotic rats.

Download Full-text

Collecting Duct Na+/K+-ATPase Activity Is Correlated with Urinary Sodium Excretion in Rat Nephrotic Syndromes

Journal of the American Society of Nephrology ◽

10.1681/asn.v114604 ◽

2000 ◽

Vol 11 (4) ◽

pp. 604-615 ◽

Cited By ~ 6

Author(s):

GEORGES DESCHÊNES ◽

ALAIN DOUCET

Keyword(s):

Nephrotic Syndrome ◽

Atpase Activity ◽

Sodium Excretion ◽

Collecting Duct ◽

Urinary Sodium ◽

Sodium Balance ◽

Brattleboro Rats ◽

Sodium Retention ◽

Puromycin Aminonucleoside ◽

Stimulation Of

Abstract. In puromycin aminonucleoside (PAN)-treated nephrotic rats, sodium retention is associated with increased Na+/K+-ATPase activity in the cortical collecting ducts (CCD). This study was undertaken to determine whether stimulation of Na+/K+-ATPase in the CCD is a feature of other experimental nephrotic syndromes, whether it might be responsible for renal sodium retention, and whether it is mediated by increased plasma vasopressin levels or activation of calcineurin. For this purpose, the time courses of urinary excretion of sodium and protein, sodium balance, ascites, and Na+/K+-ATPase activities in microdissected CCD were studied in rats with PAN or adriamycin nephrosis or HgCl2nephropathy. The role of vasopressin and calcineurin in PAN nephrosis were evaluated by measuring these parameters in Brattleboro rats and in rats treated with cyclosporin or tacrolimus. Despite different patterns of changes in urinary sodium and protein excretion in the three nephrotic syndrome models, there was a linear relationship between CCD Na+/K+-ATPase activities and sodium excretion in all three cases. The results also indicated that there was no correlation between proteinuria and sodium retention, but ascites was present only when proteinuria was associated with marked reduction of sodium excretion. Finally, the lack of vasopressin in Brattleboro rats or the inhibition of calcineurin by administration of either cyclosporin or tacrolimus did not prevent development of the nephrotic syndrome in PAN-treated rats or stimulation of CCD Na+/K+-ATPase. It is concluded that stimulation of Na+/K+-ATPase in the CCD of nephrotic rats might be responsible for sodium retention and that this phenomenon is independent of proteinuria and vasopressin and calcineurin activities.

Download Full-text

Influence of captopril on fluid and electrolyte balances and adrenocortical responses during sodium deprivation in the rat

Journal of Endocrinology ◽

10.1677/joe.0.0980211 ◽

1983 ◽

Vol 98 (2) ◽

pp. 211-NP ◽

Cited By ~ 2

Author(s):

Annette McKeever ◽

J. A. Oliver ◽

I. W. Henderson ◽

Warwick Mosley

Keyword(s):

Sodium Excretion ◽

Enzyme Inhibitor ◽

Gastric Lavage ◽

Plasma Renin ◽

Urinary Sodium Excretion ◽

Zona Glomerulosa ◽

Urinary Sodium ◽

Sodium Balance ◽

Deficient Diet ◽

Angiotensin I Converting Enzyme

An angiotensin I-converting enzyme inhibitor (captopril) was given by gastric lavage at a dose of 30 mg/kg body weight per day to Long–Evans rats for a 13-day period during which they received a sodium-deficient diet. This regime was preceded by a 3-day period during which measurements were made on the animals on a sodium-replete dietary intake. Control sodium-deprived rats showed increased plasma renin activities, increased peripheral aldosterone concentrations and reduced urinary sodium excretion; they maintained positive sodium balance and the zona glomerulosa of the adrenal cortex hypertrophied. Captopril-treated sodium-deprived rats failed to reduce urinary sodium excretion sufficiently and entered a period of marked and sustained negative sodium balance. Peripheral aldosterone concentrations after 12 days of sodium deprivation in the presence of captopril treatment were similar to those of sodium-replete rats. The adrenocortical zona glomerulosa of the captopril-treated rats did not increase in size and regressive changes were noted.

Download Full-text

POTASSIUM ACCELERATES URINARY SODIUM EXCRETION DURING SALT LOADING WITHOUT STIMULATING ATRIAL NATRIURETIC POLYPEPTIDE SECRETION

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/j.1440-1681.1992.tb00417.x ◽

1992 ◽

Vol 19 (12) ◽

pp. 795-801 ◽

Cited By ~ 6

Author(s):

Masayuki Mano ◽

Akira Sugawara ◽

Yasuo Nara ◽

Kazuwa Nakao ◽

Ryoichi Horie ◽

...

Keyword(s):

Sodium Excretion ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Salt Loading ◽

Atrial Natriuretic Polypeptide ◽

Atrial Natriuretic

Download Full-text

Neurohumoral modulators and sodium balance in experimental heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.264.4.h1187 ◽

1993 ◽

Vol 264 (4) ◽

pp. H1187-H1193 ◽

Cited By ~ 1

Author(s):

D. Villarreal ◽

R. H. Freeman ◽

R. A. Johnson

Keyword(s):

Heart Failure ◽

Sodium Excretion ◽

Plasma Renin ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Sodium Balance ◽

Renal Nerves ◽

Av Fistula ◽

Before And After ◽

High Output Heart Failure

The acute and chronic interactions of the renal nerves, atrial natriuretic factor (ANF), and mineralocorticoids for the regulation of sodium balance were examined in dogs with an arteriovenous (AV) fistula and the syndrome of high-output heart failure (HOHF) (n = 6). After the AV fistula and bilateral renal denervation, the animals avidly retained sodium for 5-7 days and then regained sodium balance for the subsequent 3 wk. This compensation was associated with the sustained elevations of plasma ANF and the normalization of plasma renin. Subsequent administration of deoxycorticosterone acetate (DOCA) for 10 days produced consistent sodium retention despite additional elevations in plasma ANF. All of these responses were similar to previous studies in AV fistula dogs with intact renal nerves. In a separate part of the study, the renal actions of acute synthetic ANF infusions were examined in these renal-denervated AV fistula dogs before and after DOCA. In the pre-DOCA experiments, ANF infusions at 15, 30, and 100 ng.kg-1.min-1 produced dose-related increases in urinary sodium excretion and significant elevations in creatinine clearance. In the presence of DOCA, urinary sodium excretion was markedly attenuated during identical ANF infusions. The composite results suggest that mineralocorticoids have an important modulatory role for the regulation of sodium balance in experimental HOHF. However, compared with earlier studies in compensated AV fistula dogs with intact renal nerves, the present studies demonstrate that blockade of efferent renal sympathetic nerve activity can restore the natriuretic expression of acute elevations in circulating ANF.

Download Full-text

Pathogenesis of Salt Retention in Dogs with Chronic Bile-Duct Ligation

Clinical Science ◽

10.1042/cs0620065 ◽

1982 ◽

Vol 62 (1) ◽

pp. 65-70 ◽

Cited By ~ 6

Author(s):

C. Chaimovitz ◽

U. Alon ◽

O. S. Better

Keyword(s):

Bile Duct ◽

Sodium Excretion ◽

Control Period ◽

Extracellular Volume ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Sodium Balance ◽

Sodium Retention ◽

Plasma Aldosterone Concentration ◽

Duct Ligation

1. The present study investigates the role of mineralocorticoids in the pathogenesis of salt retention and ascites in dogs with chronic ligation of the common bile duct (CBDL). 2. After CBDL the natriuretic response to an intravenous sodium load [0.9% sodium chloride solution (150 mmol/l): saline; 10% of body weight] was markedly depressed. Urinary sodium excretion was 285 ± 62 vs 960 ± 58 μmol/min in the control period before CBDL (P < 0.001). This antinatriuresis was associated with a significant rise in plasma aldosterone concentration, from 52.5 ± 5.5 pg/ml before CBDL to 177 ± 50 pg/ml after CBDL (P < 0.02). Ascites was present in all salt-retaining CBDL dogs. 3. Bilateral adrenalectomy resulted in disappearance of ascites and in a rise in the natriuretic response to extracellular volume expansion. Urinary sodium excretion was 770 ± 124 μmol/min, a value significantly higher than in the CBDL dogs with intact adrenals (P < 0.001). Sodium balance studies in the adrenalectomized CBDL dogs during chronic deoxycorticosterone acetate (DOCA) treatment (25 mg/day) showed that in these animals there was failure to escape from the mineralocorticoid-induced sodium retention. Glomerular filtration rate and renal plasma flow did not change during the studies. 4. The present evidence supports the thesis that sodium retention in the CBDL dog results from a dual mechanism: (a) excess of circulating aldosterone and (b) an extra-adrenal factor which prevents escape from the salt-retaining effect of mineralocorticoids, in the CBDL dogs, thereby perpetuating the antinatriuresis in these animals.

Download Full-text

Effect of Noradrenaline on Renal Sodium and Water Handling in Euhydrated and Overhydrated Man

Clinical Science ◽

10.1042/cs0850487 ◽

1993 ◽

Vol 85 (4) ◽

pp. 487-494 ◽

Cited By ~ 8

Author(s):

Chim C. Lang ◽

Abdul R. Rahman ◽

David J. K. Balfour ◽

Allan D. Struthers

Keyword(s):

Flow Rate ◽

Sodium Excretion ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Urinary Flow Rate ◽

Sodium Reabsorption ◽

Urinary Flow ◽

Noradrenaline Infusion ◽

Plasma Vasopressin ◽

Dose Dependent

1. The renal effects of incremental doses of intravenously infused noradrenaline were evaluated in normal subjects during two different water loads, 5 ml/kg (n = 6) and 20 ml/kg (n = 9), producing conditions of euhydration and overhydration, respectively. 2. Noradrenaline infusion rates ranged from 0.015 to 0.075 μg min−1 kg−1. In the euhydrated subjects, noradrenaline caused a dose-dependent fall in urinary sodium excretion and an increase in urinary flow rate. During overhydration similar doses of noradrenaline caused a fall in urinary sodium excretion but a decrease in urinary flow rate. 3. Although there was no detectable change in glomerular filtration rate, a dose-dependent fall in effective renal plasma flow was observed in both hydration states during noradrenaline infusion. 4. Noradrenaline infusion was associated with a dose-dependent increase in proximal tubular sodium reabsorption as assessed by the lithium clearance method. Fractional reabsorption of sodium by the distal nephron was, however, unchanged by noradrenaline in both hydration states. 5. Plasma vasopressin concentration was unchanged by noradrenaline in euhydrated subjects. The renin-angiotensin-aldosterone axis was stimulated by noradrenaline in both euhydrated and overhydrated subjects. 6. Thus we conclude that plasma circulating noradrenaline has a dose-dependent antinatriuretic effect in man. The antinatriuretic effect of noradrenaline is mediated mainly at the proximal tubule in man. We have also shown that during overhydration, noradrenaline decreased urinary flow rate. In contrast, in euhydrated subjects, noradrenaline increased urinary flow rate with no accompanying changes in plasma vasopressin concentration, which suggests a direct effect of noradrenaline on the renal tubular permeability to water.

Download Full-text