The Role of Vasopressin and Urea in the Renal Concentrating Defect of Patients with Cirrhosis of the Liver

1971 ◽  
Vol 41 (5) ◽  
pp. 441-452 ◽  
Author(s):  
C. A. Vaamonde ◽  
Liliana S. Vaamonde ◽  
J. I. Presser ◽  
H. J. Morosi ◽  
E. L. Klingler ◽  
...  

1. The maximal urine osmolality in response to vasopressin during water diuresis and during hydropenia was studied in twenty patients with cirrhosis and sixteen noncirrhotic subjects under controlled dietary conditions. 2. The cirrhotic patients exhibited a significantly lower maximal urine osmolality under both experimental conditions. 3. During water diuresis decompensated and compensated cirrhotics had comparable maximal urine osmolalities after vasopressin. A decreased response of the renal tubules to vasopressin does not appear to have a significant role in the concentrating defect. 4. The cirrhotic patients had a significantly lower excretion rate of urea at high (water diuresis) and low (vasopressin antidiuresis or hydropenia) urine flow rates. The lower urine urea concentration accounted for most of the decrease observed in maximal urinary concentration. After vasopressin administration the absolute tubular reabsorption of urea was also significantly lower in cirrhotic patients. The results suggest that a decrease in the medullary urea content decreases medullary osmolality resulting in the defect in urine concentration noted in these cirrhotic patients at low urine flow rates. 5. Protein depletion or decreased urea synthesis may in part be responsible for the decreased availability of urea for the concentrating process in cirrhosis. 6. Lack of correlation between concentrating and diluting capacity in these patients suggested that decreased delivery of sodium to the distal site might not be the limiting factor common to both renal functional abnormalities observed in cirrhosis of the liver.


1985 ◽  
Vol 69 (5) ◽  
pp. 601-606 ◽  
Author(s):  
J. Buckley ◽  
E. M. Gebruers ◽  
W. J. Hall ◽  
N. M. B. Harrington

1. Intravenous vasopressin (1–3 μ-units min−1 kg−1) had an antidiuretic effect on water-loaded man and also diminished potassium excretion. As noted by others, aspirin (2.4 g) enhanced the antidiuretic effect of vasopressin, but the fall in potassium excretion was not modified by prior administration of aspirin, which makes it unlikely that the fall was due to the release of endogenous prostaglandins. 2. After terminating the infusion of vasopressin, the fall in potassium output persisted longer than the antidiuresis, which makes it unlikely that the antikaliuretic effect of vasopressin is secondary to its effect on urine flow. 3. The unchanged antikaliuretic effect of vasopressin after aspirin treatment, together with its persistence after terminating the infusion, suggest the possible existence of vasopressin-mediated potassium absorption in the distal nephron in certain circumstances. 4. Aspirin administration had specific effects of its own in water-loaded man. It decreased both the water diuresis and sodium excretion but did not alter potassium excretion or urine osmolality.



1961 ◽  
Vol 200 (2) ◽  
pp. 400-404 ◽  
Author(s):  
Joseph H. Perlmutt

Conventional clearance techniques were used to study the renal response to vasopressin (5–100 mu/hr.) infused for 2 1/2 hours into anesthetized (pentobarbital), surgically traumatized dogs elaborating a dilute urine. Decreased urine flow, a concomitant sustained increase in Na+ excretion, increased urine osmolality, negative free-water clearance and an increased osmolal U/P ratio (>1, <2) consistently occurred during the infusion of 50 mu/hr. Urinary pH rose and HCO3–, rather than Cl–, was the predominant anion excreted. Tubular rejection of HCO3–, however, is not essential for vasopressin activity under the conditions of this investigation since antidiuresis occurred in an acidotic dog. Usually some increase in glomerular filtration rate and effective renal plasma flow were apparent during vasopressin infusion; the former change could account for the increased Na+ excretion, but it is difficult to ascribe the peculiar anion behavior to this factor. Maximum urinary concentration was not attained even with 100 mu vasopressin/hr.



1994 ◽  
Vol 267 (1) ◽  
pp. F139-F145 ◽  
Author(s):  
T. Nakanishi ◽  
Y. Takamitsu ◽  
H. Nakahama ◽  
M. Sugita

To determine the relationship between accumulation of osmolytes and maximal urinary concentration in potassium depletion, we tested the effects of experimental water diuresis or potassium depletion on osmolytes in the renal medulla of rats. Hyperosmotic stress was imposed by 4 days of water deprivation for the purpose of establishing the maximal concentrating ability or by the infusion of sodium for the purpose of loading the equal amounts of sodium to the renal medulla. In the diuresis group, water deprivation failed to increase betaine, sorbitol, and taurine contents to the same level as the untreated group, although sodium infusion increased betaine and sorbitol. In the potassium depletion group followed by water deprivation, urine osmolality (2,490 +/- 241 vs. 3,425 +/- 268 mosmol/kgH2O) and all osmolytes were significantly lower than in the untreated group. In response to hyperosmolality with sodium infusion, myo-inositol and glycerophosphorylcholine contents rose to the level of the untreated group. Medullary betaine (67.6 +/- 6.8 vs. 99.5 +/- 8.9), taurine (44.7 +/- 2.4 vs. 61.4 +/- 6.2) and sorbitol (35.6 +/- 4.4 vs. 57.0 +/- 8.4 mmol/kg protein) contents were reduced in potassium-depleted rats when the renal medulla was as hypertonic as in the untreated group. In conclusion, the processing of betaine, taurine, and sorbitol accumulation appeared to be impaired in potassium depletion.



1965 ◽  
Vol 208 (2) ◽  
pp. 397-400 ◽  
Author(s):  
H. L. White ◽  
Doris Rolf

Dogs in water diuresis, with high urine flow and low urine osmolality and sodium concentration, had papilla fluid osmolality of 398 milliosmols/kg H2O and papilla fluid sodium concentration of 116 millimolal. At 5.5 min after laparotomy and 100 mU of vasopressin intravenously, papilla fluid osmolality and sodium concentration showed no significant rise, but urine osmolality and sodium concentration had risen greatly. At longer intervals, up to 13 min, papilla osmolality rose to above 600 mM with a further rise in urine osmolality; osmotic equilibration between urine and papilla fluid was attained at about 10 min Papilla fluid sodium concentration rose after 5.5 min Cortex fluid remained isosmolal with plasma.



1995 ◽  
Vol 7 (3) ◽  
pp. 491 ◽  
Author(s):  
LM Berry ◽  
M Ikegami ◽  
E Woods ◽  
MG Ervin

The present experiments determined if increases in renal reabsorptive capacity during the transition from fetal to neonatal life are gestation dependent. Renal function was studied in chronically-catheterized fetal lambs (133 +/- 1 days; term, 145-150 days). Additionally, renal function was studied in anaesthetized, ventilated, caesarean-delivered preterm lambs (109-139 days gestation) and term lambs (148 days gestation), and in 2-day-old spontaneously-delivered term lambs. Newborns < or = 120 days old received surfactant to facilitate ventilation and maintenance of physiologic blood gases. Two hours after caesarian delivery, urine osmolality, urine flow, glomerular filtration rate (GFR), and fractional sodium excretion (FENa) values were similar for all gestations. Relative to fetal values, caesarean-delivered newborn renal values included lower urine flow rates (0.20 +/- 0.03 v. 0.05 +/- 0.01 mL min-1 kg-1), higher urine osmolalities (118 +/- 15 v. 422 +/- 16 mOsmol kg-1 H2O), and no differences in GFR or FENa. Relative to caesarean-delivered newborns, 2-day newborn renal function included higher values for GFR (0.7 +/- 0.1 v. 3.0 +/- 0.1 mL min-1 kg-1) and urine osmolality (724 +/- 32 mosmol kg-1 H2O), and lower FENa (7.0 +/- 1.5 v. 0.2 +/- 0.02%), and urine flow (0.005 +/- 0.003 mL min-1 kg-1). The 132- and 139-day animals were ventilated for 5 h and 10 h respectively; the only functional change at 10 h was a decrease in FENa (7.0 +/- 1.5 v. 2.8 +/- 0.1%). It is concluded that: (1) relative to fetal animals, renal adaptive responses in anaesthetized, ventilated newborns begin within 2 h following caesarian delivery; (2) initial adaptive responses are not gestation dependent after 109 days; and (3) the combined effects of ventilation and/or anaesthesia delay postnatal renal adaptations for at least 10 h after birth.



1992 ◽  
Vol 263 (3) ◽  
pp. F516-F526 ◽  
Author(s):  
J. Schnermann ◽  
J. N. Lorenz ◽  
J. P. Briggs ◽  
J. A. Keiser

Experiments were performed in anesthetized rats to examine the possibility that endothelin (ET) modifies renal epithelial function in addition to its well-established hemodynamic actions. Infusion of ET-3 at rates between 34 and 178 ng.kg-1.min-1 was in many cases followed by a rise in urine flow and a persistent decrease in urine osmolality, whereas glomerular filtration rate (GFR) did not significantly change. The extent of ET-induced diuresis was dependent on the response of GFR: in rats in which ET-3 infusion caused a marked reduction of GFR (greater than 70%) ET-induced diuresis was not seen, even though urine osmolality still fell significantly. From animal to animal, ET-induced changes of urine flow or GFR did not correlate significantly with the rate of ET-3 infusion. ET-1, another ET isopeptide, also produced water diuresis when administered in GFR-neutral doses. Urinary excretion of total solutes and of sodium was not significantly altered by ET-3. Infusion of vasopressin blunted the diuretic effect of ET-3, whereas ET-3-induced water diuresis was not measurably altered by chronic or acute treatment with a converting enzyme inhibitor or by acute inhibition of prostaglandin synthesis. Induction of water diuresis was not secondary to an inhibition of vasopressin secretion since it could be demonstrated in homozygous Brattleboro rats in which antidiuresis was produced by the infusion of vasopressin at a rate of 200 microU.kg-1.min-1. These data suggest that ET may be an inhibitory modulator of the hydrosmotic action of vasopressin at the level of the renal collecting duct.



1963 ◽  
Vol 204 (4) ◽  
pp. 548-554 ◽  
Author(s):  
Wolfgang Herms ◽  
Peter H. Abbrecht ◽  
Fernando Alzamora ◽  
Richard L. Malvin

The effect of different solute loads on the renal concentrating mechanism was evaluated at different glomerular filtration rates (GFR). GFR was varied by partial ureteral or arterial occlusion in dogs undergoing osmotic diuresis. A Ringer's solution was infused to which the following solutes were added so that the final concentrations of the solutes were as follows: a) 383 mm/liter mannitol + 255–285 mm/liter NaCl; b) 500 mm/liter urea; c) 193 mm/liter mannitol; d) 300 mm/liter urea + 385 mm/ liter mannitol. Steady-state values for GFR, urine flow, and urine osmolalities were obtained for the occluded and control kidneys and expressed as the ratio occluded-to-control. Changing the sodium chloride load did not alter the correlation between flow rate and urine osmolality as found in previous experiments with dogs which were not infused with additional sodium. However, variations in the urea and mannitol load did alter this relationship. The greater the mannitol load the lower was the osmolality ratio at any given GFR. The results indicate that both urea trapping and urine flow rates are important determinants of urinary concentrating ability.



1969 ◽  
Vol 26 (3) ◽  
pp. 639-654 ◽  
Author(s):  
D. G. Butler

In freshwater eels there is a significant correlation between glomerular filtration rates (GFR) and urine flow rates suggesting that changes in GFR rather than tubular water reabsorption lead to the major adjustments in urine flow rates accompanying changes in environmental salinity.Removal of the corpuscles of Stannius was not followed by a significant change in GFR indicating that an adequate (normal) effective filtration pressure is independent of a corpuscular pressor substance.In 8 of 17 Stanniectomised eels urine flow rates exceeded GFR demonstrating that, under these experimental conditions, eel renal tubules secrete water.Multiple tissue electrolyte changes followed Stanniectomy; the 75% increase in the plasma calcium concentration is of particular interest. This increase was probably due to a reduction in the net rate of calcium deposition in bone and not to a change in the renal handling of calcium.



2010 ◽  
Vol 298 (4) ◽  
pp. F962-F972 ◽  
Author(s):  
Anita T. Layton ◽  
Thomas L. Pannabecker ◽  
William H. Dantzler ◽  
Harold E. Layton

Simulations conducted in a mathematical model were used to exemplify the hypothesis that elevated solute concentrations and tubular flows at the boundary of the renal outer and inner medullas of rats may contribute to increased urine osmolalities and urine flow rates. Such elevated quantities at that boundary may arise from hyperfiltration and from inner stripe hypertrophy, which are correlated with increased concentrating activity (Bankir L, Kriz W. Kidney Int. 47: 7–24, 1995). The simulations used the region-based model for the rat inner medulla that was presented in the companion study (Layton AT, Pannabecker TL, Dantzler WH, Layton HE. Am J Physiol Renal Physiol 298: F000–F000, 2010). The simulations were suggested by experiments which were conducted in rat by Gamble et al. (Gamble JL, McKhann CF, Butler AM, Tuthill E. Am J Physiol 109: 139–154, 1934) in which the ratio of NaCl to urea in the diet was systematically varied in eight successive 5-day intervals. The simulations predict that changes in boundary conditions at the boundary of the outer and inner medulla, accompanied by plausible modifications in transport properties of the collecting duct system, can significantly increase urine osmolality and flow rate. This hyperfiltration-hypertrophy hypothesis may explain the finding by Gamble et al. that the maximum urine osmolality attained from supplemental feeding of urea and NaCl in the eight intervals depends on NaCl being the initial predominant solute and on urea being the final predominant solute, because urea in sufficient quantity appears to stimulate concentrating activity. More generally, the hypothesis suggests that high osmolalities and urine flow rates may depend, in large part, on adaptive modifications of cortical hemodynamics and on outer medullary structure and not entirely on an extraordinary concentrating capability that is intrinsic to the inner medulla.



1959 ◽  
Vol XXXII (I) ◽  
pp. 134-141 ◽  
Author(s):  
Niels A. Thorn

ABSTRACT Arginine-, lysine- and leucine-vasopressin, injected i. v. into hydrated rats or dogs caused different patterns of response in that urine osmolality fell much more slowly after the maximum increase following arginine-vasopressin, than after the other two preparations. Using 3 different parameters for antidiuretic response, arginine-vasopressin was somewhat more potent than leucine-vasopressin in both rats and dogs, considerably more potent than lysine-vasopressin in rats, and much more so in dogs.



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