Salt-Sensitivity of Volume and Blood Pressure in a Mouse with Globally Reduced ENaC γ Subunit Expression

2021 ◽  
Author(s):  
Evan C. Ray ◽  
Ashley Pitzer ◽  
Tracey Lam ◽  
Alexa Cross Jordahl ◽  
Ritam Patel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Extracellular Fluid ◽  
Body Water ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Lean Tissue ◽  
Tissue Mass ◽  
Lean Tissue Mass ◽  
Γ Subunit ◽  
Subunit Expression

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.

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 ◽  
...  
Keyword(s):  
Extracellular Fluid ◽  
Body Water ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Renal Tubules ◽  
Lean Tissue ◽  
Tissue Mass ◽  
Lean Tissue Mass ◽  
Γ Subunit ◽  
Subunit Expression

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.

scholarly journals The effects of oral sodium bicarbonate on extracellular water in patients with chronic kidney disease

2019 ◽  
pp. 04-13
Author(s):  
Colin Jones ◽  
Louise Wells ◽  
Graham Woodrow ◽  
David Ashford
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Sodium Bicarbonate ◽  
Total Body Water ◽  
Extracellular Fluid ◽  
Body Water ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Total Body ◽  
Oral Sodium

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.

Time course and magnitude of changes in total body water, extracellular fluid volume, intracellular fluid volume and plasma volume during submaximal exercise and recovery in horses

2004 ◽  
Vol 1 (2) ◽  
pp. 131-139 ◽  
Author(s):  
Michael I Lindinger ◽  
Gloria McKeen ◽  
Gayle L Ecker
Keyword(s):  
Plasma Volume ◽  
Total Body Water ◽  
Time Course ◽  
Extracellular Fluid ◽  
Submaximal Exercise ◽  
Body Water ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Intracellular Fluid ◽  
Total Body

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.

Relation of saluretic and hypotensive effects of hydrochlorothiazide in the rat

1960 ◽  
Vol 198 (1) ◽  
pp. 148-152 ◽  
Author(s):  
Sydney M. Friedman ◽  
Miyoshi Nakashima ◽  
Constance L. Friedman
Keyword(s):  
Blood Pressure ◽  
Plasma Volume ◽  
Extracellular Space ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Urinary Volume ◽  
Hypertensive Rats ◽  
Inulin Space

Hydrochlorothiazide causes a marked loss of Na and of water in both fully alimented rats and in rats deprived of food and/or water. The increased urinary volume corresponds closely to the shrinkage of the extracellular fluid volume (inulin space) but the decrease in extracellular Na is not sufficient to account for the Na excretion, suggesting that Na is withdrawn from cells and perhaps bone stores as well. The fall in blood pressure in hypertensive rats is not due to simple shrinkage of the extracellular space and plasma volume, but can be referred to the rise in Na gradient induced by withdrawal of cell sodium.

Some biochemical and physiological features of normal monkeys (Macaca radiata)

1963 ◽  
Vol 18 (6) ◽  
pp. 1231-1233 ◽  
Author(s):  
S. G. Srikantia ◽  
C. Gopalan
Keyword(s):  
Total Body Water ◽  
Body Fluid ◽  
Extracellular Fluid ◽  
Body Water ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Sodium Thiocyanate ◽  
Macaca Radiata ◽  
Hematological Indices ◽  
Total Body

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

scholarly journals Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure

2010 ◽  
Vol 298 (4) ◽  
pp. R851-R861 ◽  
Author(s):  
Alicia A. McDonough
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Flow Rate ◽  
Sodium Transport ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
The Body ◽  
Extracellular Fluid Volume ◽  
Ang Ii ◽  
Salt Diet

One-hundred years ago, Starling articulated the interdependence of renal control of circulating blood volume and effective cardiac performance. During the past 25 years, the molecular mechanisms responsible for the interdependence of blood pressure (BP), extracellular fluid volume (ECFV), the renin-angiotensin system (RAS), and sympathetic nervous system (SNS) have begun to be revealed. These variables all converge on regulation of renal proximal tubule (PT) sodium transport. The PT reabsorbs two-thirds of the filtered Na+ and volume at baseline. This fraction is decreased when BP or perfusion pressure is increased, during a high-salt diet (elevated ECFV), and during inhibition of the production of ANG II; conversely, this fraction is increased by ANG II, SNS activation, and a low-salt diet. These variables all regulate the distribution of the Na+/H+ exchanger isoform 3 (NHE3) and the Na+-phosphate cotransporter (NaPi2), along the apical microvilli of the PT. Natriuretic stimuli provoke the dynamic redistribution of these transporters along with associated regulators, molecular motors, and cytoskeleton-associated proteins to the base of the microvilli. The lipid raft-associated NHE3 remains at the base, and the nonraft-associated NaPi2 is endocytosed, culminating in decreased Na+ transport and increased PT flow rate. Antinatriuretic stimuli return the same transporters and regulators to the body of the microvilli associated with an increase in transport activity and decrease in PT flow rate. In summary, ECFV and BP homeostasis are, at least in part, maintained by continuous and acute redistribution of transporter complexes up and down the PT microvilli, which affect regulation of PT sodium reabsorption in response to fluctuations in ECFV, BP, SNS, and RAS.

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