scholarly journals Water and Electrolyte Homeostasis in a Mouse Model with Reduced ENaC Gamma Subunit Expression

2021 ◽  
Author(s):  
Evan C. Ray ◽  
Alexa Jordahl ◽  
Allison Marciszyn ◽  
Aaliyah Winfrey ◽  
Tracey Lam ◽  
...  

AbstractThe epithelial Na+ channel (ENaC) promotes the absorption of Na+ in the aldosterone-sensitive distal nephron, colon, and respiratory epithelia. Deletion of genes encoding ENaC’s subunits results in early post-natal mortality. We present initial characterization of a mouse with dramatically suppressed expression of the γ subunit. We use this hypomorphic (γmt) allele to explore the importance of ENaC’s γ subunit in homeostasis of electrolytes and body fluid volume. At baseline, γ subunit expression in γmt/mt mice is markedly suppressed in kidney and lung, while electrolytes resemble those of littermate controls. Challenge with a high K+ diet does not cause significant differences in blood K+, but provokes higher aldosterone in γmt/mt mice than controls. Quantitative magnetic resonance (QMR) measurement of body composition reveals similar baseline body water, lean tissue mass, and fat tissue mass in γmt/mt mice and controls. Surprisingly, euvolemia is sustained without significant changes in aldosterone or atrial natriuretic peptide. γmt/mt mice exhibit a more rapid decline in body water and lean tissue mass in response to a low Na+ diet than controls. Replacement of drinking water with 2% saline induces dramatic increases in body fat in both genotypes, and a selective transient increase in body water and lean tissue mass in γmt/mt mice. While ENaC in renal tubules and colon work to prevent extracellular fluid volume depletion, our observations suggest that ENaC in non-epithelial tissues may have a role in preventing extracellular fluid volume overload.

Author(s):  
Evan C. Ray ◽  
Ashley Pitzer ◽  
Tracey Lam ◽  
Alexa Cross Jordahl ◽  
Ritam Patel ◽  
...  

The epithelial Na+ channel (ENaC) promotes the absorption of Na+ in the aldosterone-sensitive distal nephron, colon, and respiratory epithelia. Deletion of genes encoding ENaC's subunits results in early post-natal mortality. We present initial characterization of a mouse with dramatically suppressed expression of ENaC's γ subunit. We used this hypomorphic (γmt) allele to explore the importance of this subunit in homeostasis of electrolytes and body fluid volume. At baseline, γ subunit expression in γmt/mt mice was markedly suppressed in kidney and lung, while electrolytes resembled those of littermate controls. Aldosterone levels in γmt/mt mice exceeded those seen in littermate controls. Quantitative magnetic resonance (QMR) measurement of body composition revealed similar baseline body water, lean tissue mass, and fat tissue mass in γmt/mt mice and controls. γmt/mt mice exhibited a more rapid decline in body water and lean tissue mass in response to a low Na+ diet than controls. Replacement of drinking water with 2% saline selectively and transiently increased body water and lean tissue mass in γmt/mt mice, relative to controls. Lower blood pressures were variably observed in γmt/mt mice on a high salt diet, compared to controls. γmt/mt also exhibited reduced diurnal blood pressure variation, a "non-dipping" phenotype, on a high Na+ diet. While ENaC in renal tubules and colon work to prevent extracellular fluid volume depletion, our observations suggest that ENaC in other tissues may participate in regulating extracellular fluid volume and blood pressure.


2004 ◽  
Vol 1 (2) ◽  
pp. 131-139 ◽  
Author(s):  
Michael I Lindinger ◽  
Gloria McKeen ◽  
Gayle L Ecker

AbstractThe purpose of the present study was to determine the time course and magnitude of changes in extracellular and intracellular fluid volumes in relation to changes in total body water during prolonged submaximal exercise and recovery in horses. Seven horses were physically conditioned over a 2-month period and trained to trot on a treadmill. Total body water (TBW), extracellular fluid volume (ECFV) and plasma volume (PV) were measured at rest using indicator dilution techniques (D2O, thiocyanate and Evans Blue, respectively). Changes in TBW were assessed from measures of body mass, and changes in PV and ECFV were calculated from changes in plasma protein concentration. Horses exercised by trotting on a treadmill for 75–120 min incurred a 4.2% decrease in TBW. During exercise, the entire decrease in TBW (mean±standard error: 12.8±2.0 l at end of exercise) could be attributed to the decrease in ECFV (12.0±2.4 l at end of exercise), such that there was no change in intracellular fluid volume (ICFV; 0.9±2.4 l at end of exercise). PV decreased from 22.0±0.5 l at rest to 19.8±0.3 l at end of exercise and remained depressed (18–19 l) during the first 2 h of recovery. Recovery of fluid volumes after exercise was slow, and characterized by a further transient loss of ECFV (first 30 min of recovery) and a sustained increase in ICFV (between 0.5 and 3.5 h of recovery). Recovery of fluid volumes was complete by 13 h post exercise. It is concluded that prolonged submaximal exercise in horses favours net loss of fluid from the extracellular fluid compartment.


1963 ◽  
Vol 18 (6) ◽  
pp. 1231-1233 ◽  
Author(s):  
S. G. Srikantia ◽  
C. Gopalan

Determinations of body-fluid spaces with antipyrine for total-body water and sodium thiocyanate for extracellular fluid volume, hematological indices, and several serum constituents in about 500 Macaca radiata monkeys revealed that most of the values obtained were very similar to values obtained in man. body fluid spaces; hematology Submitted on April 22, 1963


2019 ◽  
pp. 04-13
Author(s):  
Colin Jones ◽  
Louise Wells ◽  
Graham Woodrow ◽  
David Ashford

Background: Metabolic acidosis in chronic kidney disease (CKD) is often treated with oral sodium bicarbonate. There is limited evidence around the effects of sodium bicarbonate on extracellular fluid and blood pressure in CKD. Methods: In a double blind randomised comparison patients with stage 3-5 CKD were randomised to either oral sodium bicarbonate 1.5 g three times a day (n=18) or placebo (n=21) for 4 weeks. Assessments performed at 0 and 4 weeks included: body weight, office blood pressure and assessment for peripheral/pulmonary oedema; serum creatinine, electrolytes and venous bicarbonate; 24-hour urine for sodium excretion; extracellular fluid volume and total body water determined by sodium bromide and deuterium oxide dilution respectively; extracellular fluid volume and total body water by bioimpedance. Differences between the active and placebo groups at week 4 were analysed by ANCOVA. Results: At week 4, serum bicarbonate was higher (25.6±2.4 vs 23.3±3.1 mmol/l) and blood urea lower (14.2±5.6 vs 17.0±5.8 mmol/l) in the active treatment group. Urine sodium concentration was also higher (82.7±25.3 vs 59.0±21.9 mmol/l). Extracellular fluid volume (20.0±4.3 vs 18.0±2.9) and total body water (42.3±9.6 vs 39.0±6.8) measured by bioimpedance and total body water by deuterium dilution (41.7±8.3 vs 39.4±6.2) were significantly greater in the treatment arm at week 4. Differences in systolic and diastolic blood pressure did not reach statistical significance. Conclusions: Oral sodium bicarbonate has a biological effect and increases body water content, without evidence of a clinical consequence. This may reflect the fact that some of the ingested sodium is excreted in the urine.


1972 ◽  
Vol 43 (1) ◽  
pp. 79-90 ◽  
Author(s):  
F. Skrabal ◽  
R. N. Arnot ◽  
G. F. Joplin ◽  
T. R. Fraser

1. Simultaneous measurements of exchangeable Na+, exchangeable K+, extracellular fluid volume and total body water, with 24Na, 43K, 77Br and 3H2O, were carried out in patients with adrenocortical insufficiency due to pituitary ablation performed 1–3 months previously. 2. The first group of five patients was studied before and after withdrawal of maintenance prednisone (2·5 mg three times daily, orally). The effects of glucocorticoid withdrawal were: (a) an increase in intracellular water (all cases) and a decrease in the extracellular fluid volume (four cases) irrespective of any change in serum Na+ concentration; (b) an increase in residual (‘intracellular’) Na+ in all cases which was matched by a loss of extracellular Na+, so that total body Na+ remained unchanged, and (c) the cortisol deficiency clinical syndrome. Exchangeable K+ remained unchanged. 3. Similar measurements were obtained with two further patients during the corticosteroid withdrawal period, throughout which they were kept on a maintenance dose of deoxycorticosterone acetate, 1·0 mg twice daily sublingually. Neither the above biochemical changes nor the cortisol deficiency syndrome developed. 4. The shift into the cells of water and Na+ may depend on the same defect caused by glucocorticoid deficiency, and may be the cause of the cortisol deficiency syndrome.


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