THE EFFECT OF FUROSEMIDE, A NEW DIURETIC AGENT, ON RENAL CONCENTRATING AND DILUTING MECHANISMS

1966 ◽  
Vol 44 (1) ◽  
pp. 129-137 ◽  
Author(s):  
Peter A. F. Morrin

The effect of a new diuretic, Furosemide, has been studied in normal subjects undergoing both osmotic and water diuresis. A marked increase in the excretion of sodium and water was observed, the latter amounting to 30% of the glomerular filtrate. In the hydropenic subjects the drug virtually abolished negative free water clearance, which indicates that the site of action is in the ascending limb of Henle's loop. In the water-loaded subjects, free water clearance was decreased but not abolished, which suggests that urinary dilution distal to the ascending limb of Henle's loop is not significantly impaired by the diuretic.

1989 ◽  
Vol 256 (4) ◽  
pp. R892-R897 ◽  
Author(s):  
A. M. Moses

Eleven hydrated normal subjects were infused with hypertonic saline so that plasma osmolalities (POsmol) ranged from 280 to 306 mosmol/kg. Linear relationships were calculated between POsmol and plasma and urine arginine vasopressin (AVP) in the 11 individual subjects. There was an excellent linear correlation between POsmol and plasma and urine AVP, with the latter as concentration or rate of excretion. The highest correlation coefficient occurred when urine AVP was expressed as microunits of AVP per 100 milliliters of glomerular filtrate. The smallest coefficient of variation of the slopes occurred when urine AVP was expressed as microunits of AVP per minute. The osmotic thresholds obtained by abscissal intercepts from relating POsmol to urine AVP per minute or per 100 milliliters of glomerular filtrate were 285.9 and 285.5 mosmol/kg, respectively. These values did not differ from the mean osmotic threshold obtained by traditional free water clearance changes (285.8 mosmol/kg). Analysis of the relationship between plasma osmolality and plasma AVP resulted in the greatest variation in slope and osmotic threshold, with the latter being significantly lower than that obtained by free water clearance changes. The data also demonstrated a much more rapid rise of urine than of plasma AVP under the stated conditions of osmotic stimulation.


1973 ◽  
Vol 45 (4) ◽  
pp. 469-477
Author(s):  
E. J. Dorhout Mees ◽  
H. de Graaf

1. Free water clearance (CH2O) was measured in sixteen normal subjects and twenty-five patients with uncomplicated hypertension at different levels of salt intake. 2. In normal subjects CH2O and Na+ excretion were related thus: log Na+ excretion = 0·1685 + 0·1508 × CH2O. At a given value for Na+ excretion the standard deviation for CH2O was ±1·5 ml min−1. 3. The mean value for the ratio CH2O/creatinine clearance was higher in the hypertensive patients than in controls at all levels of Na+ excretion. 4. Most previous studies reporting decreased values for CH2O in hypertension can be explained by the exponential relationship between CH2O and Na+ excretion.


1972 ◽  
Vol 42 (4) ◽  
pp. 423-432 ◽  
Author(s):  
John R. Gill ◽  
Catherine S. Delea ◽  
F. C. Bartter

1. The response to an infusion of 4% (w/v) fructose in water was determined in fifteen women on a daily sodium intake of 100 mEq/day. The results were compared with those obtained during a similar infusion on another day after treatment with deoxycorticosterone (20 mg/day; seven subjects), or spironolactone (200 mg/day; eight subjects), for 1 day before the day of study. 2. Treatment with deoxycorticosterone significantly (P < 0·01) decreased sodium excretion (from a mean value of 391 to 192 μEq/min) and urine flow rate (from 14·3 to 12·4 ml min−1 100 ml−1 of glomerular filtrate) without a change in urinary osmolality or the clearance of inulin. The steroid also increased the fractional reabsorption of sodium at the diluting segment of the nephron, but this increase in reabsorption was not sufficient to compensate for the decrease in delivery of sodium to the site, so that absolute free-water clearance decreased. 3. Treatment with spironolactone significantly (P < 0·01) increased sodium excretion (from 349 to 437 μEq/min) and urine flow rate (from 12·5 to 14·4 ml min−1 100 ml−1 of glomerular filtrate) with essentially no change in urinary osmolality or in inulin clearance. Spironolactone also decreased the fractional reabsorption of sodium at the diluting segment of the nephron, but the degree of inhibition of reabsorption was not sufficient to prevent an increase in free-water clearance as a result of increased delivery of sodium to the site. 4. The findings support the concept that changes in circulating aldosterone can alter the renal excretion of sodium in man by affecting its reabsorption in the proximal tubule as well as in the distal tubule.


1962 ◽  
Vol 202 (6) ◽  
pp. 1131-1135 ◽  
Author(s):  
E. Lovell Becker ◽  
H. Earl Ginn

Free water excretion (Chh2o = V - Cosm) was studied in unanesthetized dogs. This parameter of urine dilution was defined by superimposing an osmotic diuresis upon a water diuresis. Sodium sulfate (1.5%) gave the smallest free water clearance and sodium chloride (0.95%) the greatest, urea (1.65%) and mannitol (5.0%) being intermediary in their effects. Observed free water clearances were never maximal and, when plotted as Cosm vs. V, gave a slope of less than one. Two mercurial diuretics, meralluride and mercaptomerin, gave intermediary values for free water. Meralluride caused an early increase in free water clearance because of the theophylline incorporated in the compound. Later results were similar to those with mercaptomerin, both compounds producing free water clearances approaching a maximal rate.


2021 ◽  
Vol 19 (4) ◽  
Author(s):  
О.А. Olenovych

The aim of the study – to explore the role of the renin-angiotensin-aldosteronesystem (RAAS) in the disturbance of ionoregulatory renal function in alloxan-inducedexperimental diabetes mellitus (EDM).Material and methods. The experiments were carried out on 78 white non-linearmature male rats with 11-, 26- and 46-day long alloxan-induced EDM with underlyingpharmacological blockade of RAAS by administration of kaptopril. The study ofionoregulating function of the kidneys was provided by the clearance method under thecondition of water 2-hour diuresis.Results. Pharmacological blockade of RAAS in rats with alloxan-induced EDM causedan intensification of natriuresis at all stages of the experiment: increased urinaryconcentration of sodium ions, its excretion and clearance. On the 11th day of EDM, thesodium filtration charge increased with the development of hyponatremia, proximal anddistal sodium reabsorption standardized in volume of glomerular filtrate (GF) decreased,kaliuresis was suppressed, and sodium-free water clearance elevated. In case of 26-daylong EDM, the sodium filtration charge decreased, its absolute and relative reabsorption,the distal sodium reabsorption standardized by GF increased. Kaliuresis increased. In46-day long EDM, the sodium filtration charge decreased, and hyponatremia enhanced.Absolute and relative sodium reabsorption reduced due to both – proximal and distal.Kaliuresis augmented, the clearance of sodium-free water declined.Conclusions. The increase in urinary sodium loss during the 11-day EDM is stipulatedby glomerular hyperfiltration, causing a functional weakening of the tubulotubularbalance and relative dysfunction of the distal segment of the nephron, emphasizing therenoprotective effect of RAAS on ionoregulatory function of the kidneys. The decrease inthe total reabsorption potential of the tubular segment of the nephron in the dynamics ofEDM development reflects on the proximal tubules, and preserved tubulotubular balancecertifies functional intactness of the distal tubules in 26-day long EDM. RAAS pathologicalactivation and attenuation of the renal blood flow autoregulation by tubuloglomerularfeedback may serve as an initiating factor in the development of tubular disorders in 26-day long alloxan diabetes with following progression in 46-day long EDM.


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