Effects of aspirin on renal sodium excretion, blood pressure, and plasma and extracellular fluid volume in salt-loaded rats

The aim of this study was to examine the changes in the concentration of plasma immunoreactive atrial natriuretic factor (iANF) that occur in response to expansion or depletion of the extracellular fluid volume in conscious dogs. The plasma iANF concentration was also measured postprandially after the ingestion of a meal containing 125 meq of sodium. Postprandial plasma iANF increased 45% (P less than 0.05) above the base-line concentration, and this increase was accompanied by a brisk natriuresis. After a low-sodium meal, however, plasma iANF and sodium excretion failed to increase. The plasma iANF concentration increased from 57 +/- 5 to 139 +/- 36 pg/ml (P less than 0.05) immediately after volume expansion with intravenous isotonic saline infusion (2.5% body wt) administered over a 30-min period; plasma iANF remained elevated at 90 +/- 14 pg/ml (P less than 0.05) for an additional 30 min before returning toward preinfusion levels. Plasma iANF decreased 45% from 78 +/- 17 to 43 +/- 7 pg/ml (P less than 0.05) in response to the administration of ethacrynic acid (2.0 mg/kg, iv bolus) that produced an estimated 15% depletion of intravascular volume. In additional experiments the infusion of synthetic alpha-human ANF at 100 and 300 ng X kg-1 X min-1 increased (P less than 0.05) both the plasma iANF concentration and the urinary excretion of iANF. This study demonstrates that the secretion of ANF is consistently influenced by changes in the extracellular fluid volume. Furthermore, the results support the concept that ANF functions to increase postprandial sodium excretion following the ingestion of a high-sodium meal.

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The Interrelationship between ECF Volume and ECF Anion Composition in the Regulation of Sodium Excretion

Clinical Science ◽

10.1042/cs0390475 ◽

1970 ◽

Vol 39 (4) ◽

pp. 475-487

Author(s):

J. J. Cohen ◽

J. A. Chazan ◽

S. Garella

Keyword(s):

Hydrochloric Acid ◽

Sodium Bicarbonate ◽

Sodium Excretion ◽

Extracellular Fluid ◽

Progressive Increase ◽

Fluid Volume ◽

Extracellular Fluid Volume ◽

Volume Depletion ◽

Anion Composition ◽

Bicarbonate Infusion

1. The interrelationship between extracellular fluid volume and extracellular anion composition as determinants of sodium excretion was studied in thirty-four dogs. In six, hypovolaemia, hypochloraemia and hyperbicarbonataemia were induced by the administration of ethacrynic acid and a low chloride diet. Isotonic sodium bicarbonate was then infused resulting in a progressive increase in sodium excretion. After 3 h while continuing the sodium bicarbonate infusion, an infusion of hydrochloric acid was given in order to return extracellular anion composition towards normal. This resulted in a prompt fall in sodium excretion without a change in GFR. 2. Ten studies were performed to determine whether this hydrochloric acid-induced enhancement of sodium conservation depends upon the presence of volume depletion and sodium avidity or whether it could also be demonstrated under circumstances of volume expansion. In these studies, hypervolaemia, hypochloraemia, hyperbicarbonataemia and a brisk natriuresis were induced by infusing isotonic sodium bicarbonate into normal dogs. The addition of hydrochloric acid returned anion composition to normal and, as before, resulted in a prompt suppression of sodium excretion despite continued sodium loading and enhanced glomerular filtration. 3. Results obtained from three related protocols (six animals each) confirmed that hypochloraemia and hyperbicarbonataemia were the necessary prerequisite conditions for this effect of hydrochloric acid in volume expanded animals. We interpret these findings as evidence that the response of the kidney to changes in extracellular fluid volume may be significantly affected by changes in the extracellular concentration of physiologic anions.

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Role of renal arterial pressure in the regulation of extracellular volume in conscious dogs

Clinical Science ◽

10.1042/cs0820247 ◽

1992 ◽

Vol 82 (3) ◽

pp. 247-254 ◽

Cited By ~ 2

Author(s):

Gabriele Kaczmarczyk ◽

Klaus Schröder ◽

Dirk Lampe ◽

Rainer Mohnhaupt

Keyword(s):

Body Weight ◽

Arterial Pressure ◽

Sodium Excretion ◽

Urine Volume ◽

Extracellular Fluid ◽

Fluid Volume ◽

Extracellular Fluid Volume ◽

Conscious Dogs ◽

Central Venous ◽

Infusion Period

1. This study in conscious dogs examined the quantitative effects of a reduction in the renal arterial pressure on the renal homoeostatic responses to an acute extracellular fluid volume expansion. 2. Seven female beagle dogs were chronically instrumented with two aortic catheters, one central venous catheter and a suprarenal aortic cuff, and were kept under standardized conditions on a constant high dietary sodium intake (14.5 mmol of Na+ day−1 kg−1 body weight). 3. After a 60 min control period, 0.9% (w/v) NaCl was infused at a rate of 1 ml min−1 kg−1 body weight for 60 min (infusion period). Two different protocols were applied during the infusion period: renal arterial pressure was maintained at 102 ± 1 mmHg by means of a servo-feedback control circuit (RAP-sc, 14 experiments) or was left free (RAP-f, 14 experiments). 4. During the infusion period, in the RAP-sc protocol as well as in the RAP-f protocol, the mean arterial pressure increased by 10 mmHg, the heart rate increased by 20 beats/min, the central venous pressure increased by 4 cmH2O and the glomerular filtration rate (control 5.1 ± 0.3 ml min−1 kg−1 body weight, mean ± sem) increased by 1 ml min−1 kg−1. 5. Plasma renin activity [control 0.85 ± 0.15 (RAP-f) and 1.08 ± 0.23 (RAP-sc) pmol of angiotensin I h−1 ml−1] decreased similarly in both protocols. 6. Renal sodium excretion, fractional sodium excretion and urine volume increased more in the RAP-f experiments than in the RAP-sc experiments (P<0.05), renal sodium excretion from 8.2 to 70.1 (RAP-f) and from 7.7 to 47.4 (RAP-sc) μmol min−1 kg−1 body weight, fractional sodium excretion from 1.1 to 8.0 (RAP-f) and from 1.0 to 5.4 (RAP-sc)% and urine volume from 39 to 586 (RAP-f) and from 38 to 471 (RAP-sc) μl min−1 kg−1 body weight. 7. In the RAP-f experiments as well as in the RAP-sc experiments, urinary sodium excretion increased with expansion of the extracellular fluid volume, which increased by a maximum of 21% (fasting extracellular fluid volume: 206 ± 4 ml/kg body weight, six dogs, 28 days). 8. The increase in renal arterial pressure contributed significantly to the renal homoeostatic response, as 21% less urine and 31% less sodium were excreted when the extracellular fluid volume was expanded and the renal arterial pressure was kept constant below control pressure rather than being allowed to rise. The differences in sodium and water excretion were mainly due to the effect of renal arterial pressure on tubular reabsorption. However, the striking increase in sodium and urine excretion which occurred despite the reduction in renal arterial pressure emphasizes the importance of other homoeostatic factors involved in body fluid regulation.

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Relation of saluretic and hypotensive effects of hydrochlorothiazide in the rat

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1960.198.1.148 ◽

1960 ◽

Vol 198 (1) ◽

pp. 148-152 ◽

Cited By ~ 19

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.

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

AJP Renal Physiology ◽

10.1152/ajprenal.00559.2020 ◽

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.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00002.2010 ◽

2010 ◽

Vol 298 (4) ◽

pp. R851-R861 ◽

Cited By ~ 120

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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