Urinary Sodium Excretion and Proximal Tubule Reabsorption in Rats with 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.

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Hormonal determinants of sodium excretion in rats with experimental high-output heart failure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.254.5.r776 ◽

1988 ◽

Vol 254 (5) ◽

pp. R776-R784 ◽

Cited By ~ 10

Author(s):

J. Winaver ◽

A. Hoffman ◽

J. C. Burnett ◽

A. Haramati

Keyword(s):

Heart Failure ◽

Sodium Excretion ◽

Plasma Renin ◽

Urinary Sodium Excretion ◽

Plasma Aldosterone ◽

Base Line ◽

Sham Control ◽

Renal Handling ◽

High Output Heart Failure ◽

High Output

The present study evaluates the inter-relationship between the alteration in atrial natriuretic factor (ANF) and the renal handling of Na in rats with chronic aortocaval (a-v) fistula, an experimental model of congestive heart failure. Balance studies in these animals showed two distinct patterns of Na excretion: some rats developed progressive Na retention [urinary sodium excretion (UNaV) less than 100 mueq/24 h], whereas others compensated and returned to normal Na balance (UNaV greater than 1,200 mueq/24 h). Base-line plasma ANF levels were equally elevated in Na-retaining and compensated rats with a-v fistula (588 +/- 70 vs. 621 +/- 114 pg/ml, P, NS). However, the response of the two groups to exogenous administration of synthetic rat ANF-(101-126) in incremental doses varied greatly. ANF infusion increased the fractional Na excretion (FENa) in compensated animals from 0.12 +/- 0.03 to 2.6 +/- 0.5%, whereas the rise in FENa in Na-retaining animals was markedly blunted (0.11 +/- 0.06 to 0.89 +/- 0.35%). A similar pattern of ANF action was observed on the glomerular filtration rate and urine flow. The blunted response to ANF in the Na-retaining animals was associated with a marked increase in plasma renin activity (PRA) (35.6 +/- 6.9 vs. 4.5 +/- 0.7 ng ANG I.ml-1.h-1 in sham control rats, P less than 0.05) and plasma aldosterone levels (729.3 +/- 28.2 vs. 42.6 +/- 18.4 ng/dl in sham control rats, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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Captopril enhances renal responsiveness to ANF in dogs with compensated high-output heart failure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.262.3.r509 ◽

1992 ◽

Vol 262 (3) ◽

pp. R509-R516 ◽

Cited By ~ 1

Author(s):

D. Villarreal ◽

R. H. Freeman ◽

R. A. Johnson

Keyword(s):

Heart Failure ◽

Urinary Sodium Excretion ◽

Sodium Balance ◽

Angiotensin Converting Enzyme Inhibition ◽

Systemic Hemodynamic ◽

Av Fistula ◽

High Output Heart Failure ◽

Converting Enzyme Inhibition ◽

Control Infusion ◽

High Output

The systemic hemodynamic, hormonal, and renal effects of chronic angiotensin-converting enzyme inhibition (CEI) with captopril and the responses to synthetic atrial natriuretic factor (ANF) infusions in the presence and absence of captopril were examined in normal dogs (n = 6) and in dogs with an arteriovenous (AV) fistula and compensated high-output heart failure (n = 6). This experimental model is characterized by normalization of the circulating renin-angiotensin-aldosterone system (RAAS) and persistent elevations in central filling pressures and plasma ANF. In both normal and AV-fistula dogs, oral captopril for 1 wk at 35 mg.kg-1.day-1 in three divided doses produced progressive reductions in arterial and atrial pressures (P less than 0.05), plasma ANF (P less than 0.05), and aldosterone (P less than 0.05). After 1-2 days of a modest increase in urinary sodium excretion (UNaV) (P less than 0.05), all of the dogs regained and maintained sodium balance during captopril administration. On the 8th day of the captopril regimen, synthetic ANF was infused at 15 and 30 ng.kg-1.min-1 for 75-min periods each. Control infusion experiments were performed in the same animals before captopril administration. The normal dogs exhibited dose-related elevations in UNaV (P less than 0.05) that were not augmented with captopril (P greater than 0.05). In contrast, in the AV-fistula dogs the observed renal unresponsiveness to synthetic ANF in the control experiments was reversed with chronic CEI, and ANF-induced UNaV achieved levels comparable to those obtained in the normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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Urinary sodium evaluation: the missing target for diuretic treatment optimization in acute heart failure patients? Letter regarding the article ‘Clinical importance of urinary sodium excretion in acute heart failure’

European Journal of Heart Failure ◽

10.1002/ejhf.1814 ◽

2020 ◽

Vol 22 (10) ◽

pp. 1933-1933

Author(s):

Alessandro Galluzzo ◽

Maurizio Bertaina ◽

Simone Frea

Keyword(s):

Heart Failure ◽

Acute Heart Failure ◽

Sodium Excretion ◽

Clinical Importance ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Treatment Optimization ◽

Diuretic Treatment ◽

Heart Failure Patients

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The control of sodium excretion

AJP Renal Physiology ◽

10.1152/ajprenal.1978.235.3.f163 ◽

1978 ◽

Vol 235 (3) ◽

pp. F163-F173 ◽

Cited By ~ 2

Author(s):

H. E. de Wardener

Keyword(s):

Proximal Tubule ◽

Sodium Excretion ◽

Collecting Duct ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Sodium Balance ◽

Sodium Reabsorption ◽

Loop Of Henle ◽

Salt Loading ◽

Large Fluctuations

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.

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Clinical importance of urinary sodium excretion in acute heart failure

European Journal of Heart Failure ◽

10.1002/ejhf.1753 ◽

2020 ◽

Vol 22 (8) ◽

pp. 1438-1447 ◽

Cited By ~ 6

Author(s):

Kevin Damman ◽

Jozine M. Ter Maaten ◽

Jenifer E. Coster ◽

Jan A. Krikken ◽

Vincent M. Deursen ◽

...

Keyword(s):

Heart Failure ◽

Acute Heart Failure ◽

Sodium Excretion ◽

Clinical Importance ◽

Urinary Sodium Excretion ◽

Urinary Sodium

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Urinary sodium excretion and risk of heart failure in men and women in the EPIC-Norfolk study

European Heart Journal ◽

10.1093/eurheartj/eht308.p2478 ◽

2013 ◽

Vol 34 (suppl 1) ◽

pp. P2478-P2478

Author(s):

R. Pfister ◽

G. Michels ◽

S. Sharp ◽

R. Luben ◽

N. Wareham ◽

...

Keyword(s):

Heart Failure ◽

Sodium Excretion ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Men And Women

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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.

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Effects of renal denervation on postprandial sodium excretion in experimental heart failure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.266.5.r1599 ◽

1994 ◽

Vol 266 (5) ◽

pp. R1599-R1604 ◽

Cited By ~ 2

Author(s):

D. Villarreal ◽

R. H. Freeman ◽

R. A. Johnson ◽

J. C. Simmons

Keyword(s):

Heart Failure ◽

Sodium Excretion ◽

Atrial Natriuretic Factor ◽

High Salt ◽

Renal Nerves ◽

Av Fistula ◽

Natriuretic Factor ◽

High Output Heart Failure ◽

Filtered Load ◽

High Output

The hormonal, hemodynamic and renal excretory changes after an oral load of sodium were examined in renal-denervated dogs with an arteriovenous (AV) fistula and the syndrome of compensated high-output heart failure. After ingestion of a meal containing 125 meq of sodium, the total postprandial urinary sodium excretion and fractional sodium excretion were approximately twofold higher in the renal-denervated AV fistula dogs, compared with a control group with intact renal nerves (P < 0.05). The postprandial elevations in right atrial pressure, plasma atrial natriuretic factor, and filtered load of sodium were similar in the two groups (P > 0.05). Mean arterial pressure and plasma renin activity remained unchanged from baseline in the two subsets of animals (P > 0.05). In the renal-denervated AV fistula dogs, ingestion of a low-salt meal containing 2-3 meq of sodium produced elevations in creatinine clearance and filtered load of sodium of similar magnitude to the high-salt meal. However, the increases in sodium excretion and plasma atrial natriuretic factor were modest and inconsistent. These results demonstrate that the renal nerves play an important modulatory role for postprandial sodium metabolism after a high-salt meal in experimental compensated high-output heart failure. It is suggested that the renal nerves attenuate the expression of postprandial natriuretic mechanisms via a direct tubular mechanism of action.

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