Mechanism of the Impaired Natriuretic Response to Frusemide during Sodium Depletion: A Micropuncture Study in Rats

1996 ◽  
Vol 91 (3) ◽  
pp. 299-305 ◽  
Author(s):  
D. G. Shirley ◽  
S. J. Walter ◽  
R. J. Unwin

1. The nephron sites involved in the blunted natriuretic response to frusemide during sodium depletion were investigated using micropuncture techniques in anaesthetized rats. 2. Glomerular filtration rate was lower, and fractional sodium reabsorption in the proximal convoluted tubule higher, in sodium-depleted than in sodium-replete rats. Consequently, sodium delivery to the loop of Henle was reduced (by approximately 35%) in the sodium-depleted animals. Intravenous frusemide (2.5 mg h−1 kg−1; urinary water and electrolyte losses replaced) had no effect on glomerular filtration rate or proximal tubular sodium reabsorption in either group. 3. The inhibitory effect of intravenous frusemide on fractional sodium reabsorption in the nephron segments constituting the loop of Henle (measured by free-flow micropuncture) was attenuated during sodium depletion. However, when loops of Henle were microperfused at identical rates with artificial late proximal tubular fluid, no difference in the responses of sodium-depleted and sodium-replete rats to intraluminal frusemide (10−5 mol/l) could be detected. 4. In sodium-replete animals, the increased load of sodium delivered from the loop of Henle during frusemide administration resulted in a lowering of fractional sodium reabsorption in the distal tubule. In contrast, in sodium-depleted rats given frusemide, fractional distal sodium reabsorption tended to increase, so that values in the two groups of frusemide-treated animals were markedly different (0.30 ±0.04 versus 0.51 ±0.03). 5. It is concluded that the blunted natriuretic response to frusemide during sodium depletion results from at least three factors: a reduced sodium delivery to the loop of Henle; a reduced inhibitory effect of frusemide on fractional sodium reabsorption in the loop of Henle, which may be a consequence of the reduced sodium load; and enhanced fractional reabsorption of sodium in the distal tubule, which partially buffers the diuretic-induced increase in sodium delivery from the loop.

1979 ◽  
Vol 57 (5) ◽  
pp. 427-434 ◽  
Author(s):  
S. J. Walter ◽  
J. F. Laycock ◽  
D. G. Shirley

1. Renal function in anaesthetized Brattleboro rats with hereditary hypothalamic diabetes insipidus was studied with micropuncture techniques before, and 1–3 h after, a single injection of hydrochlorothiazide. 2. In rats given hydrochlorothiazide and kept in sodium and water balance, total glomerular filtration rate and superficial nephron filtration rate were similar to values in control animals, whereas fractional fluid reabsorption in the proximal tubule (as evidenced by tubular fluid/plasma inulin concentration ratios) was slightly, but significantly, reduced. This suggests that hydrochlorothiazide may have a small direct inhibitory effect on proximal tubular reabsorption. 3. When rats were given hydrochlorothiazide and the resultant extra urinary sodium losses were not replaced, there was a marked antidiuresis. In these animals total glomerular filtration rate was reduced by 23% and superficial nephron filtration rate by 27% when compared with values in control rats. Fractional proximal tubular fluid reabsorption increased significantly whereas absolute proximal fluid reabsorption was unaffected. 4. It is concluded that the reduction in body sodium which follows acute hydrochlorothiazide administration over-rides any inhibitory effect of the drug on proximal tubular reabsorption, and leads instead to an increase in fractional fluid reabsorption at this site. This effect, combined with the fall in glomerular filtration rate, results in a greatly reduced delivery of fluid to the more distal nephron segments, and is probably largely responsible for the observed antidiuresis.


1980 ◽  
Vol 239 (3) ◽  
pp. F206-F214 ◽  
Author(s):  
C. R. Silva-Netto ◽  
M. de Mello Aires ◽  
G. Malnic

The anterior part of the lateral hypothalamus was stimulated by injection of carbachol through a stereotaxically implanted cannula in the rat. Re-collection micropuncture experiments showed that this procedure, which leads to diuresis and natriuresis with only transient changes in glomerular filtration rate and renal plasma flow, reduced the TF/P inulin ratio along proximal and distal tubules without significant alteration of single nephron glomerular filtration rate in most experimental groups. Fractional proximal sodium reabsorption was significantly reduced from 0.54 +/- 0.02 to 0.34 +/- 0.05. Treatment with DOCA, vasopressin, and oxytocin caused natriuresis, but additional hypothalamic stimulation (HS) led to further reduction in TF/P inulin ratio and proximal fractional sodium reabsorption from 0.42 +/- 0.03 to 0.33 +/- 0.03. Fluid transport across proximal and distal epithelium was also studied by the split-droplet method. It was markedly reduced in both segments after HS. During hormone treatment only distal segments showed reduction of fluid transport by HS. These experiments indicate that HS caused inhibition of fluid transport in the proximal and distal tubule. This effect was only partly due to the liberation of neurohypophysial hormones, since during their administration an additional effect of HS was still observed.


1989 ◽  
Vol 256 (5) ◽  
pp. F810-F813 ◽  
Author(s):  
D. E. Kohan ◽  
C. A. Merli ◽  
E. E. Simon

Interleukin 1 (IL-1) has been demonstrated to elicit an increase in renal sodium excretion. This effect occurs in the absence of any increase in the filtered load of sodium, raising the possibility of an IL-1-mediated decrease in tubule sodium reabsorption. To localize the nephron segment(s) responsible for the natriuretic effect of IL-1, we performed micropuncture experiments on rats. Intravenous IL-1 administration caused a marked increase in sodium excretion that was not accompanied by changes in glomerular filtration rate or systemic blood pressure. Single-nephron glomerular filtration rate and fractional and absolute delivery of sodium to the late proximal and mid-distal tubule were not affected by IL-1. Fractional delivery of sodium to the early and late papillary collecting duct, however, was significantly enhanced by IL-1 administration. Sodium reabsorption was inhibited along the papillary collecting duct. These findings demonstrate that the natriuretic effect of IL-1 is due, at least in part, to inhibition of collecting duct sodium reabsorption.


1986 ◽  
Vol 250 (4) ◽  
pp. F590-F595 ◽  
Author(s):  
N. L. Wong ◽  
S. J. Whiting ◽  
C. L. Mizgala ◽  
G. A. Quamme

A micropuncture study of the rabbit was performed to evaluate the function of the superficial nephron. The mean glomerular filtration rate of the left micropunctured kidney was 4.0 +/- 0.8 ml/min. The concentration profile of electrolytes within the proximal tubule was similar to that of species previously investigated except for potassium. The mean tubular fluid (TF)-ultrafilterable (UF) concentration ratios were as follows: sodium, 1.01 +/- 0.03; chloride, 1.14 +/- 0.04; calcium, 1.12 +/- 0.04; magnesium, 1.47 +/- 0.08; and phosphate, 0.94 +/- 0.09, with a mean TF-plasma (P) inulin concentration ratio of 1.78 +/- 0.14 (n = 32). The TF/UF potassium value significantly increased in association with TF/P inulin to a mean value of 1.26 +/- 0.06. Accordingly, 29% of the filtered potassium was reabsorbed in the superficial proximal tubule compared with 43% of the filtered sodium. The loop of Henle reabsorbed 55-60% of the filtered sodium, chloride, and calcium, whereas considerably less magnesium (33%) was reabsorbed. Segments beyond the distal tubule collection site reabsorbed little of the delivered magnesium, which supports the notion that the loop of Henle is the principal segment accounting for adjustments in magnesium balance. These studies indicate that the superficial nephron of the rabbit performs similar to other species reported, except potassium reabsorption is significantly less in the proximal convoluted tubule.


1990 ◽  
Vol 79 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Michael Allon ◽  
Charles B. Pasque ◽  
Mariano Rodriguez

1. Eight nephrotic patients were studied in order to evaluate the effects of acute changes in renal plasma flow and glomerular filtration rate on renal solute and water handling, in the absence of plasma volume expansion. 2. The subjects were studied first after the administration of captopril, a manoeuvre that increased renal plasma flow without a significant change in glomerular filtration rate, and a second time after receiving combined therapy with captopril and ibuprofen, a manoeuvre that decreased glomerular filtration rate without a significant change in renal plasma flow. 3. After captopril therapy, despite the increase in renal plasma flow, there was no significant change in proximal sodium reabsorption (as estimated from fractional lithium reabsorption), urine volume or urine osmolality. 4. The decrease in glomerular filtration rate observed after the administration of captopril plus ibuprofen was associated with decreases in fractional excretion of sodium and urine volume, and an increase in urine osmolality. The changes in these parameters of tubular function were proportionate to the changes in glomerular filtration rate. Fractional proximal sodium reabsorption increased substantially. 5. These observations suggest that, in the absence of plasma volume expansion, an increase in renal plasma flow does not increase sodium or water excretion by the nephrotic kidney. Moreover, during acute decreases in glomerular filtration rate, glomerulotubular balance appears to be disrupted, resulting in disproportionately high rates of proximal tubule sodium reabsorption.


1962 ◽  
Vol 202 (4) ◽  
pp. 768-772 ◽  
Author(s):  
Charles Toussaint ◽  
Pierre Vereerstraeten

K+ excretion rate was measured at normal as well as at rising plasma K+ concentration in intact, in K-depleted, and in acetazolamide-treated dogs submitted to acute blood pH changes. The results indicate that, for any given value of glomerular filtration rate, K+ excretion rate is determined by at least three factors: 1) plasma K+ concentration, 2) blood pH level, and 3) presumably, the H+ gradient across the luminal border of the distal tubule. The data further suggest that most of the filtered K+ is reabsorbed by the proximal tubule, even in conditions of high filtered loads.


1997 ◽  
Vol 92 (4) ◽  
pp. 397-407 ◽  
Author(s):  
JAN Carstens ◽  
Kaare T. Jensen ◽  
Erling B. Pedersen

1. The renal efficacy of urodilatin in humans has only been partly investigated. It is unknown whether intravenously infused urodilatin has an effect on sodium reabsorption in both the proximal and distal part of the nephron. 2. Twelve healthy subjects participated in this double-blind, placebo-controlled study in a crossover design. They received, in a randomized order, a short term (60 min) infusion of urodilatin in three different doses (10, 20 and 40 ng min−1 kg−1 of body weight) and placebo. Renal haemodynamics were estimated by clearance technique with radioactive tracers, and proximal tubular handling of sodium was evaluated by lithium clearance. 3. The 20 ng min−1 kg−1 dose increased the urinary sodium excretion and urinary flow rate compared with the effects of placebo. It increased the glomerular filtration rate and decreased the effective renal plasma flow. In addition, the dose increased the lithium clearance compared with placebo, but did not significantly change the fractional excretion of lithium. On the other hand, it markedly decreased the distal fractional reabsorption of sodium. It also had a suppressive effect on renin secretion. The systemic arterial blood pressure was unchanged, but the dose increased the pulse rate and the haematocrit. The highest dose (40 ng min−1 kg−1) induced a wide variation in the natriuretic and diuretic responses, probably due to a blood-pressure-lowering effect. 4. We conclude, that the urodilatin dose of 20 ng min−1 kg−1 of body weight was most efficacious in this short-term infusion study, and that it had potent natriuretic and diuretic qualities, probably due to stimulation of the glomerular filtration rate and inhibition of sodium reabsorption in the distal part of the nephron.


1981 ◽  
Vol 241 (6) ◽  
pp. F612-F617
Author(s):  
E. J. Braun ◽  
D. R. Roy ◽  
R. L. Jamison

A micropuncture study of Perognathus penicillatus, a small rodent native to the deserts of the southwestern United States was performed to evaluate the function of the superficial nephron. Data are reported for 12 animals of 17 g average body wt. Mean glomerular filtration rate was 475 +/- 73 microliter X min-1 X g kidney wt-1. Urine osmolality averaged 1,154 +/- 197 mosmol/kg H2O. Single nephron glomerular filtration rate averaged 43 nl X min-1 X g kidney wt-1 in the proximal tubule and 48 in the distal tubule, values that are not significantly different. In terms of the filtered load remaining unreabsorbed at the end of the accessible proximal tubule, the average percentages were 46 water, 48 total solute, 45 sodium, 56 phosphorus, 62 potassium, 71 magnesium, and 54 calcium. The concentrations of potassium and magnesium in fluid samples increased significantly along the proximal tubule. Approximately at the midpoint of the distal tubule, fractional delivery of water, 13.1%, was greater than that for total solute, 10%, or sodium, 7%, indicating that the intervening segment of nephron reabsorbed solute and sodium in excess of water. The function of the superficial nephron resembles that of species previously investigated except for potassium reabsorption in the proximal convoluted tubule.


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