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.

Sodium chloride, extracellular fluid volume, and blood pressure regulation

1986 ◽  
Vol 251 (4) ◽  
pp. F563-F575 ◽  
Author(s):  
J. M. Hamlyn ◽  
M. P. Blaustein
Keyword(s):  
Blood Pressure ◽  
Extracellular Fluid ◽  
Indirect Evidence ◽  
Fluid Volume ◽  
The Body ◽  
Extracellular Fluid Volume ◽  
Functional Changes ◽  
Secondary Defect ◽  
Pressure Volume Relationship ◽  
Hypertensive Diseases

Data from humans and experimental animals indicate that hypertensive diseases triggered by extracellular fluid volume expansion are characterized, in their chronic phases, by relatively normal blood volume (BV) and heightened pressure-volume relationship may be viewed as corresponding to a condition of "virtual hypervolemia," where BV is inappropriately "high" relative to blood pressure. The limited data available on the phasic relationship between these variables indicate that the BV expansion appears to be a prerequisite to alterations in vascular ion metabolism, that both of these changes precede the rise in blood pressure, and that structures within the central nervous system may be a critical link between the body fluid volumes and vascular functional changes. In contrast, hypertensive diseases triggered by secretion of pressor agents or their precursors appear to be characterized in their chronic phases by low BV. These relationships and the associated alterations in plasma aldosterone and renin levels are summarized for a variety of clinical syndromes, including essential hypertension and pregnancy-induced hypertension. Direct or indirect evidence of a primary or secondary defect in renal function is apparent as an underlying event in many of these diseases.

RENAL RESPONSE TO INFUSION OF ISOTONIC RINGER-LOCKE SOLUTION: EFFECT OF HYPOPHYSECTOMY

1977 ◽  
Vol 74 (2) ◽  
pp. 193-204
Author(s):  
J. T. BAKER ◽  
S. SOLOMON
Keyword(s):  
Body Weight ◽  
Proximal Tubule ◽  
Volume Expansion ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Water Reabsorption ◽  
Locke Solution ◽  
Hypophysectomized Rats ◽  
Distal Tubules

A comparison of the renal response to extracellular fluid volume expansion (5% body weight) was made between 25 normal and 25 chronically hypophysectomized rats. The extracellular fluid compartments averaged 25 ± 1% of body weight in both groups during control, fasted conditions. Extracellular fluid volume increased to 33 ± 1% in hypophysectomized and 34 ± 2% in normal rats during expansion, based on body weight. In addition, filtration fraction was similar in both normal and hypophysectomized rats during control (0·29 ± 0·03 and 0·26 ± 0·02 respectively) and infusion of Ringer–Locke solution (0·24 ± 0·05 and 0·27 ± 0·05 respectively). Thus our results cannot be explained by differences in the degree of expansion or failure to increase filtration in proportion to plasma flow. During infusion of isotonic Ringer–Locke solution, fractional water and sodium excretion both averaged 5·1% in normal rats and only 1·3% and 0·82% respectively in hypophysectomized rats. The ratio of single nephron to whole kidney filtration rate failed to increase as much in hypophysectomized compared with normal rats. Significant increases of fractional volume excretion occurred in both groups by the end of the accessible portion of the proximal tubule. However, fractional water reabsorption was depressed significantly more in normal (mean = 37%) than in hypophysectomized rats (mean = 19%). Fractional water reabsorption in distal tubules was similar in both groups during expansion. Arterial pressure was lower in hypophysectomized rats under control conditions, but showed similar changes during expansion compared with normal rats. Passage time decreased significantly in all groups after Ringer–Locke infusion, but remained prolonged in hypophysectomized rats in proximal and distal tubules. It is concluded that chronic hypophysectomy results in a less efficient renal excretion of volume and sodium chloride load. This inefficiency appears to be related in part to (1) failure of the proximal tubule to depress water reabsorption to a level equivalent to normal rats, and (2) failure to re-distribute flow to outer cortical glomeruli following extracellular fluid volume expansion in hypophysectomized rats.

scholarly journals Proximal tubule NHE3 activity is inhibited by beta-arrestin-biased angiotensin II type 1 receptor signaling

2015 ◽  
Vol 309 (8) ◽  
pp. C541-C550 ◽  
Author(s):  
Carla P. Carneiro de Morais ◽  
Juliano Z. Polidoro ◽  
Donna L. Ralph ◽  
Thaissa D. Pessoa ◽  
Maria Oliveira-Souza ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
G Protein ◽  
Extracellular Fluid ◽  
The Body ◽  
Type I ◽  
Ang Ii ◽  
Receptor Signaling

Physiological concentrations of angiotensin II (ANG II) upregulate the activity of Na+/H+ exchanger isoform 3 (NHE3) in the renal proximal tubule through activation of the ANG II type I (AT1) receptor/G protein-coupled signaling. This effect is key for maintenance of extracellular fluid volume homeostasis and blood pressure. Recent findings have shown that selective activation of the beta-arrestin-biased AT1 receptor signaling pathway induces diuresis and natriuresis independent of G protein-mediated signaling. This study tested the hypothesis that activation of this AT1 receptor/beta-arrestin signaling inhibits NHE3 activity in proximal tubule. To this end, we determined the effects of the compound TRV120023, which binds to the AT1R, blocks G-protein coupling, and stimulates beta-arrestin signaling on NHE3 function in vivo and in vitro. NHE3 activity was measured in both native proximal tubules, by stationary microperfusion, and in opossum proximal tubule (OKP) cells, by Na+-dependent intracellular pH recovery. We found that 10−7 M TRV120023 remarkably inhibited proximal tubule NHE3 activity both in vivo and in vitro. Additionally, stimulation of NHE3 by ANG II was completely suppressed by TRV120023 both in vivo as well as in vitro. Inhibition of NHE3 activity by TRV120023 was associated with a decrease in NHE3 surface expression in OKP cells and with a redistribution from the body to the base of the microvilli in the rat proximal tubule. These findings indicate that biased signaling of the beta-arrestin pathway through the AT1 receptor inhibits NHE3 activity in the proximal tubule at least in part due to changes in NHE3 subcellular localization.

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.

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.

Lithium clearance in man: Effects of dietary salt intake, acute changes in extracellular fluid volume, amiloride and frusemide

1987 ◽  
Vol 73 (6) ◽  
pp. 645-651 ◽  
Author(s):  
J. C. Atherton ◽  
R. Green ◽  
S. Hughes ◽  
V. McFall ◽  
J. A. Sharples ◽  
...  
Keyword(s):  
Volume Expansion ◽  
Salt Intake ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
High Salt ◽  
Extracellular Fluid Volume ◽  
Lithium Clearance ◽  
Dietary Salt ◽  
Salt Diet ◽  
Dietary Salt Intake

1. The effects of amiloride and frusemide on lithium clearance were studied during changes in dietary sodium chloride intake and during infusion of 0.9% NaCl in normal human volunteers. 2. Lithium and fractional lithium clearances were less on the low than on the high salt diet. Values for the medium salt diet were intermediate. Acute extracellular fluid volume expansion with 0.9% NaCl infusion and extracellular fluid volume contraction 3–4 h after intravenous frusemide caused lithium and fractional lithium clearances to increase and decrease respectively. 3. Amiloride caused small changes in lithium and fractional lithium clearances on a low salt diet, but was without effect when salt intake was medium or high. 4. Increases in lithium clearance occurred immediately after frusemide irrespective of dietary salt intake and in subjects infused with 0.9% NaCl. Only in salt-depleted subjects did frusemide cause a substantial increase in fractional lithium clearance. Changes induced under other circumstances were small. 5. It is concluded that the lithium clearance method for assessment of proximal tubule salt and water re-absorption can be used with some degree of confidence in certain circumstances (medium and high salt intake as well as in acute volume expansion) but may not be reliable when dietary salt intake is low.

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