Effects of subpicomolar changes in vasopressin on urinary concentration

1988 ◽  
Vol 255 (6) ◽  
pp. R940-R945 ◽  
Author(s):  
M. Baerwolff ◽  
P. Bie
Keyword(s):  
Free Water ◽  
Urine Osmolality ◽  
Urinary Concentration ◽  
Metabolic Clearance ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Control Series ◽  
Water Load ◽  
Small Increments ◽  
Solute Excretion

The possibility that small amounts of vasopressin (AVP) reduce water excretion without affecting solute excretion was investigated in conscious dogs. AVP was infused intravenously for 120 min at rates of 2 and 5 pg.min-1.kg body wt-1 during water diuresis elicited by a sustained water load of 2% body wt. During control experiments urine osmolality was constantly approximately 60 mosmol/kgH2O; during AVP infusions it increased by factors of 1.36 (P less than 0.01) and 2.12 (P less than 0.01), respectively, concomitant with 39 +/- 6 and 61 +/- 7% reductions in urine flow. Osmolar and free water clearances decreased significantly. Sodium excretion did not change; changes in potassium excretion during AVP were similar to those of the control series, i.e., a gradual decline. During AVP, 5 pg.min-1. kg-1, creatinine and urea clearances decreased (25 +/- 2 and 31 +/- 7%, respectively, both P less than 0.01). With the assumption of metabolic clearance rates of AVP of 15-40 ml.min-1.kg body wt-1, the increase in plasma AVP during the infusion of 2 pg.min-1.kg body wt-1 was 5-13 X 10(-14) M. It is concluded that small increments in plasma AVP may reduce glomerular filtration rate and that with increasing levels of AVP in plasma 1) reduction of free water clearance, 2) reduction in urea clearance, and 3) natriuresis-kaliuresis occur in that order. Apparently AVP cannot reduce water excretion without changing the rate of excretion of solutes.

Effects of terlipressin on the aquaretic system: evidence of antidiuretic effects

2008 ◽  
Vol 295 (5) ◽  
pp. F1295-F1300 ◽  
Author(s):  
Aleksander Krag ◽  
Flemming Bendtsen ◽  
Erling Bjerregaard Pedersen ◽  
Niels-Henrik Holstein-Rathlou ◽  
Søren Møller
Keyword(s):  
Free Water ◽  
Urine Osmolality ◽  
Refractory Ascites ◽  
Plasma Sodium ◽  
Receptor Stimulation ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Water Load ◽  
Before And After ◽  
Placebo Infusion

The vasopressin analog terlipressin is believed to cause vasoconstriction selectively by V1 receptor stimulation. However, a possible antidiuretic effect by V2 receptor stimulation has never been ruled out. Twenty-two patients with ascites, including seven with refractory ascites, were included. The subjects were studied during a 400 ml/h oral water load before and after infusion of 2 mg of terlipressin (18 patients) or placebo infusion (4 patients). Effects on the V2 receptors were assessed by evaluating aquaporin (AQP)2 excretion, free water clearance (C[Formula: see text]), urine osmolality (Uosm), and fractional distal water excretion (DFeH2O). After terlipressin the excretion of AQP2 increased by 89% [144 ng/mmol creatinine, 95% confidence interval (CI) 73–214 ng/mmol creatinine, P = 0.001]. C[Formula: see text] decreased 1.05 ml/min (from 0.17 to −0.89 ml/min, P = 0.001), and DFeH2O decreased 37% (19 vs. 12; 95% CI 2–11, P = 0.01). Uosm increased by 27% (93 mosmol/kgH2O, 95% CI 23–164 mosmol/kgH2O, P = 0.02). Plasma sodium decreased 1.1 mmol/l ( P < 0.01). An increase in AQP2 excretion and a decrease in C[Formula: see text] and distal water excretion after terlipressin despite water loading is a clear indication of activation of the antidiuretic system (V2 receptor effect).

Nonosmotic release of vasopressin and renal aquaporins in impaired urinary dilution in hypothyroidism

2005 ◽  
Vol 289 (4) ◽  
pp. F672-F678 ◽  
Author(s):  
Yung-Chang Chen ◽  
Melissa A. Cadnapaphornchai ◽  
Jianhui Yang ◽  
Sandra N. Summer ◽  
Sandor Falk ◽  
...  
Keyword(s):  
Protein Expression ◽  
Renal Cortex ◽  
Free Water ◽  
Urine Osmolality ◽  
Protein Abundance ◽  
Oral Gavage ◽  
Water Excretion ◽  
Urinary Osmolality ◽  
Water Load ◽  
Fluid Delivery

The purpose of this study was to examine protein expression of renal aquaporins (AQP) and ion transporters in hypothyroid (HT) rats in response to an oral water load compared with controls (CTL) and HT rats replaced with l-thyroxine (HT+T). Hypothyroidism was induced by aminotriazole administration for 10 wk. Body weight, water intake, urine output, solute and urea excretion, and serum and urine osmolality were comparable among the three groups at the conclusion of the 10-wk treatment period. One hour after oral gavage of water (50 ml/kg body wt), HT rats demonstrated significantly less water excretion, higher minimal urinary osmolality, and decreased serum osmolality compared with CTL and HT+T rats. Despite the hyposmolality, plasma vasopressin concentration was elevated in HT rats. These findings in HT rats were associated with an increase in protein abundance of renal cortex AQP1 and inner medulla AQP2. AQP3, AQP4, and the Na-K-2Cl cotransporter were also increased. Moreover, 1 h following the oral water load, HT rats demonstrated a significant increase in the membrane-to-vesicle fraction of AQP2 by Western blot analysis. The defect in urinary dilution in HT rats was reversed by the V2 vasopressin antagonist OPC-31260. In conclusion, impaired urinary dilution in HT rats is primarily compatible with the nonosmotic release of vasopressin and increased protein expression of renal AQP2. The impairment of maximal solute-free water excretion in HT rats, however, appears also to involve diminished distal fluid delivery.

Mechanism of Action of Indomethacin in Tubular Defects

PEDIATRICS ◽  
1985 ◽  
Vol 75 (3) ◽  
pp. 501-507
Author(s):  
Mario Usberti ◽  
Carmine Pecoraro ◽  
Stefano Federico ◽  
Bruno Cianciaruso ◽  
Bruna Guida ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Diabetes Insipidus ◽  
Mechanism Of Action ◽  
Nephrogenic Diabetes Insipidus ◽  
Fanconi Syndrome ◽  
Free Water ◽  
Synthesis Inhibitor ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Water Load

Indomethacin, a potent prostaglandin synthesis inhibitor, has been proven to be effective in a number of tubular defects characterized by enhanced prostaglandin (namely, prostaglandin E2 (PGE2) production, but its mechanism of action is poorly understood. To elucidate further the mechanism(s) by which indomethacin reverses the abnormal tubular functions, five children with different tubular defects (nephrogenic diabetes insipidus, three cases; Fanconi syndrome, one case; and pseudohypoaldosteronism, one case) were treated with indomethacin. Indomethacin, 1 mg/kg every eight hours, was given for 1 week to all children and then was given chronically to four of the children who responded to the drug. Its use was suspended in a 10 year-old-boy with nephrogenic diabetes insipidus because it proved ineffective. To assess the site along the nephron where indomethacin affects the solute and water excretion, an acute water load study was performed in three responsive children before and during the treatment. Indomethacin did not significantly alter the glomerular filtration rate but was effective in reducing diuresis and levels of urinary sodium and potassium excretion. In the child with Fanconi syndrome, indomethacin was also effective in controlling the urinary loss of phosphate, urate, glucose, and bicarbonate. Results of the water load studies show that indomethacin decreases the delivery of solute from the proximal tubule, reduces the fractional free water clearance, and increases the urine-plasma osmolar ratio. The rate of urinary excretion of prostaglandin E2 was high in all five children; it decreased below normal values in four of them after 1 week of treatment. In the child with nephrogenic diabetes insipidus who did not respond to indomethacin therapy, prostaglandin E2 excretion decreased but the rate remained higher than normal. These results suggest that indomethacin induces retention of solute and water mainly through an enhanced proximal tubular reabsorption.

Ovine fetal renal and hormonal responses to changes in plasma epinephrine

1991 ◽  
Vol 260 (1) ◽  
pp. R82-R89
Author(s):  
M. G. Ervin ◽  
R. Castro ◽  
D. J. Sherman ◽  
M. G. Ross ◽  
J. F. Padbury ◽  
...  
Keyword(s):  
Renal Function ◽  
Sodium Excretion ◽  
Free Water ◽  
Urine Osmolality ◽  
Plasma Epinephrine ◽  
Epinephrine Infusion ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Fourfold Increase ◽  
Fetal Plasma

Circulating epinephrine alters atrial natriuretic factor (ANF) and arginine vasopressin (AVP) secretion, and all three hormones influence renal function. To quantify the relationships among fetal plasma epinephrine levels, fetal ANF and AVP secretion, and fetal renal function, six chronically catheterized fetal lambs (132 +/- 1 days gestation) received successive 40-min epinephrine infusions (0.1, 0.4, and 1.8 micrograms.min-1.kg-1). The second epinephrine infusion dose evoked significant increases in urine flow (V; 0.7 +/- 0.2 to 1.2 +/- 0.2 ml/min), free water clearance (CH2O; 0.3 +/- 0.1 to 0.7 +/- 0.1 ml/min), glomerular filtration rate (GFR; 3.9 +/- 0.7 to 5.4 +/- 0.8 ml/min), fractional water excretion (V/CH2O; 19 +/- 3 to 25 +/- 2%), mean arterial pressure (MAP; 45 +/- 3 to 51 +/- 4 mmHg), and a 94% increase in plasma ANF levels. A fourfold increase in the infusion dose significantly increased osmolar clearance (0.3 +/- 0.1 to 0.6 +/- 0.1 ml/min), sodium excretion (28 +/- 8 to 53 +/- 13 mueq/min), and plasma AVP levels (2.4 +/- 0.5 to 6.4 +/- 2.4 pg/ml) with no additional effect on V, CH2O, GFR, V/GFR, MAP, or plasma ANF levels. Urine osmolality and fractional sodium excretion did not change in response to epinephrine infusion. Our results demonstrate that epinephrine infusion stimulates fetal ANF secretion and to a lesser extent AVP secretion and significantly influences fetal renal function.

Hyponatraemia in quadriplegic patients

1988 ◽  
Vol 75 (4) ◽  
pp. 441-444 ◽  
Author(s):  
David J. Leehey ◽  
Alicia A. Picache ◽  
Gary L. Robertson
Keyword(s):  
Arginine Vasopressin ◽  
Fluid Intake ◽  
Plasma Osmolality ◽  
Free Water ◽  
Plasma Sodium ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Water Load ◽  
Daily Urine ◽  
Plasma Arginine

1. Studies were performed in five hyponatraemic (plasma sodium 129 ±1.6 mmol/l; plasma osmolality 268 ±3.0 mosmol/kg) quadriplegic patients in order to elucidate its aetiology. Five age- and sex-matched healthy subjects served as controls. 2. Daily urine volumes were high (4454 ± 624 ml) in the quadriplegic patients secondary to habitually increased fluid intake. 3. All quadriplegic patients had suppressed plasma arginine vasopressin levels (< 0.8 pmol/l) and were able to form dilute urine after a water load (20 ml/kg). However, free water clearance and the ability to excrete the water load were frequently impaired, and these defects were associated with reductions in both osmolar clearance and delivery of filtrate to the distal diluting sites of the nephron. 4. During hypertonic saline (5%, w/v, NaCl) infusion, plasma arginine vasopressin rose progressively before plasma osmolality reached the normal range, consistent with a resetting of the osmostat. 5. We conclude that hyponatraemia in quadriplegic patients is related to an intrarenal defect in water excretion and resetting of the osmostat coupled with increased fluid intake.

Renal activity of vasopressin in anesthetized dogs

1961 ◽  
Vol 200 (2) ◽  
pp. 400-404 ◽  
Author(s):  
Joseph H. Perlmutt
Keyword(s):  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Free Water ◽  
Urine Osmolality ◽  
Urine Flow ◽  
Urinary Concentration ◽  
Urinary Ph ◽  
Free Water Clearance ◽  
Anesthetized Dogs ◽  
Sustained Increase

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.

scholarly journals Increased susceptibility to thiazide-induced hyponatremia in the elderly.

1994 ◽  
Vol 5 (4) ◽  
pp. 1106-1111
Author(s):  
B A Clark ◽  
R P Shannon ◽  
R M Rosa ◽  
F H Epstein
Keyword(s):  
Free Water ◽  
Urine Osmolality ◽  
The Elderly ◽  
Serum Osmolality ◽  
Elderly Subjects ◽  
Free Water Clearance ◽  
Water Load ◽  
Water Loading ◽  
Healthy Elderly ◽  
Two Parameters

Hyponatremia is a common cause of morbidity in the elderly, and thiazide diuretics are often implicated. Eleven healthy young volunteers, eight healthy old volunteers, and five elderly patients with a history of thiazide-induced hyponatremia were studied to determine susceptibility to thiazide-induced hypoosmolality in age. Each of the healthy subjects ingested a water load (20 mL/kg) after 3 days of hydrochlorothiazide (HCTZ) (100 mg/day) or placebo. Although there were no differences in minimum Uosm between young and old, the healthy old had lower hourly free water clearances (CH2O) as compared with the young and a greater decline in serum osmolality in response to water loading (P < 0.05). HCTZ impaired minimum urine osmolality and CH2O and delayed recovery of serum osmolality after the water load in both healthy young and old (P < 0.005, placebo versus HCTZ), but the impairment in the latter two parameters was greater in the healthy elderly (P < 0.05, young versus old). Vasopressin levels were not different between healthy young and old (1.9 +/- 0.3 versus 2.0 +/- 1.0 pm with placebo; 3.0 +/- 0.7 versus 4.4 +/- 1.0 with HCTZ). Five of the young subjects were restudied after the addition of ibuprofen (400 mg thrice daily) to the thiazide and placebo regimens. Creatinine clearance was not changed, but free water clearance and serum osmolality after water loading were significantly reduced to a degree similar to that seen in the elderly subjects on the thiazide regimen (P < 0.05), suggesting an important role for renal prostaglandins in the defense against hyponatremia.

Antidiuretic effect of subnormal levels of arginine vasopressin in normal humans

1990 ◽  
Vol 259 (1) ◽  
pp. R53-R60 ◽  
Author(s):  
L. J. Andersen ◽  
J. L. Andersen ◽  
H. J. Schutten ◽  
J. Warberg ◽  
P. Bie
Keyword(s):  
Arginine Vasopressin ◽  
Free Water ◽  
Human Kidney ◽  
Urine Osmolality ◽  
Significant Rise ◽  
Constant Infusion ◽  
Free Water Clearance ◽  
Water Load ◽  
Normal Humans ◽  
Renal Responses

The renal responses to 120-min infusions of arginine vasopressin (AVP) were investigated in healthy volunteers undergoing water diuresis induced by an oral water load of 20 ml/kg body wt. AVP at 1 pg.min-1.kg-1 (approximately 10(-15) mol.min-1.kg-1) decreased urine flow (12.2 +/- 1.7 to 7.4 +/- 1.5 ml/min) and free water clearance (9.7 +/- 1.5 to 4.8 +/- 1.4 ml/min) and increased urine osmolality (Uosmol; 71 +/- 6 to 115 +/- 15 mosmol/kgH2O); 5 pg.min-1.kg-1 elicited pronounced antidiuresis (14.4 +/- 0.9 to 0.9 +/- 0.3 ml/min) with maximal Uosmol of 621 +/- 95 mosmol/kg. In response to 25 pg.min-1.kg-1, maximal Uosmol was 869 +/- 38 mosmol/kg. Responses developed gradually and stabilized within the 2nd h of infusion. AVP at 1 and 5 pg.min-1.kg-1 was without effect for at least 20 min. Only 25 pg.min-1.kg-1 caused a significant rise in plasma AVP (1.2 +/- 0.2-2.0 +/- 0.1 pg/ml), and with this dose sodium excretion decreased. The rates of K+ excretion, as well as plasma aldosterone and atrial natriuretic peptide concentrations, were unaffected by AVP. It is concluded that the human kidney is sensitive to changes in the rate of secretion of AVP of less than 1 pg.min-1.kg-1 and that the maximal change occurs after 1-2 h of constant infusion. It is estimated that the rate of infusion of AVP required to produce isosmolar urine during overhydration is approximately 3 pg.min-1.kg-1.

Effect of sodium fluoride on concentrating and diluting ability in the rat

1977 ◽  
Vol 232 (4) ◽  
pp. F335-F340 ◽  
Author(s):  
J. D. Wallin ◽  
R. A. Kaplan
Keyword(s):  
Cyclic Amp ◽  
Urine Volume ◽  
Free Water ◽  
Urine Osmolality ◽  
Inhibitory Effect ◽  
Sprague Dawley ◽  
Free Water Clearance ◽  
Sprague Dawley Rats ◽  
Direct Inhibitory Effect ◽  
Hereditary Hypothalamic Diabetes Insipidus

Mechanisms for the concentrating defect produced by fluoride were examined in the rat. Free-water clearance at all levels of delivery was normal after 5 days of chronic fluoride administration in the hereditary hypothalamic diabetes insipidus rat. In the Sprague-Dawley rats, during moderate fluoride administration (120 micronmol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased, but after exogenous vasopressin, volume decreased and osmolality and cyclic AMP increased appropriately. During larger daily doses of fluoride (240 micronmol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin. These data suggest that ascending limb chloride reabsorption is unaltered by fluoride administration; in the presence of sufficient fluoride, collecting tubular cells apparently do not generate cyclic AMP or increase permeability appropriately in response to vasopressin. The postulated defect is felt to be due to either a decrease in ATP availability or to a direct inhibitory effect of fluoride on the vasopressin-dependent cyclic AMP generating system.

Osmoregulation of thirst and vasopressin during normal menstrual cycle

1988 ◽  
Vol 254 (4) ◽  
pp. R641-R647 ◽  
Author(s):  
T. J. Vokes ◽  
N. M. Weiss ◽  
J. Schreiber ◽  
M. B. Gaskill ◽  
G. L. Robertson
Keyword(s):  
Menstrual Cycle ◽  
Luteal Phase ◽  
Plasma Osmolality ◽  
Free Water ◽  
Urine Osmolality ◽  
Free Water Clearance ◽  
Vasopressin Release ◽  
Plasma Vasopressin ◽  
Normal Menstrual Cycle ◽  
Basal Plasma

Changes in osmoregulation during normal menstrual cycle were examined in 15 healthy women. In 10 women, studied repetitively during two consecutive menstrual cycles, basal plasma osmolality, sodium, and urea decreased by 4 mosmol/kg, 2 meq/l, and 0.5 mM, respectively (all P less than 0.02) from the follicular to luteal phase. Plasma vasopressin, protein, hematocrit, mean arterial pressure, and body weight did not change. In five other women, diluting capacity and osmotic control of thirst and vasopressin release were assessed in follicular, ovulatory, and luteal phases. Responses of thirst and/or plasma vasopressin, urine osmolality, osmolal and free water clearance to water loading, and infusion of hypertonic saline were normal and similar in the three phases. However, the plasma osmolality at which plasma vasopressin and urine osmolality were maximally suppressed as well as calculated osmotic thresholds for thirst and vasopressin release were lower by 5 mosmol/kg in the luteal than in the follicular phase. This lowering of osmotic thresholds for thirst and vasopressin release, which occurs in the luteal phase, is qualitatively similar to that observed in pregnancy and should be taken into account when studying water balance and regulation of vasopressin secretion in healthy cycling women.

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