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.

Molecular analysis of impaired urinary diluting capacity in glucocorticoid deficiency

2006 ◽  
Vol 290 (5) ◽  
pp. F1135-F1142 ◽  
Author(s):  
Weidong Wang ◽  
Chunling Li ◽  
Sandra N. Summer ◽  
Sandor Falk ◽  
Melissa A. Cadnapaphornchai ◽  
...  
Keyword(s):  
Urinary Output ◽  
Protein Abundance ◽  
Oral Gavage ◽  
Water Excretion ◽  
Urinary Osmolality ◽  
Water Load ◽  
Water Loading ◽  
Apical Trafficking ◽  
Glucocorticoid Deficiency ◽  
Type 3

Urinary diluting ability and protein abundance of renal aquaporins (AQPs) and ion transporters in glucocorticoid-deficient (GD) rats were examined at baseline and in response to oral water loading. Rats underwent bilateral adrenalectomy followed by aldosterone (GD) or aldosterone + dexamethasone (CTL) replacement. Before oral water loading, urinary output was significantly decreased and urinary osmolality (Uosm) was increased in GD compared with CTL rats. Protein abundance of inner medullary AQP2 (148 ± 18%), phosphorylated AQP2 (pAQP2, 156 ± 13%), and AQP3 (145 ± 8%) was significantly upregulated in GD compared with CTL rats (all P < 0.05). GD rats also demonstrated a marked reduction in urinary Na+ excretion compared with pair-fed CTL rats. Na+-K+-2Cl− cotransporter, Na+/H+ exchanger type 3, and cortical β- and γ-subunits of the epithelial Na+ channel were significantly upregulated in GD rats. At 1 h after an acute water load (40 ml/kg by oral gavage), GD rats demonstrated a decrease in percent water excretion (5 ± 1 vs. 33 ± 9%, P < 0.01) and urinary output (33 ± 12 vs. 250 ± 65 μl·kg−1·min−1, P < 0.05) and an increase in Uosm (1,894 ± 292 vs. 316 ± 92 mosmol/kgH2O, P < 0.001) compared with CTL rats. Plasma AVP was increased (1.6 ± 0.2 vs. 0.9 ± 0.2 pg/ml, P < 0.05), as was protein expression of inner medullary AQP2 (149 ± 5%) and pAQP2 (177 ± 9%, P < 0.01), in GD compared with CTL rats; apical expression of AQP2 was maintained in GD rats. The vasopressin V2 receptor antagonist OPC-31260 increased percent water excretion and urinary output and reduced Uosm compared with vehicle-treated GD rats. OPC-31260 also reversed the increased abundance and apical trafficking of inner medullary AQP2 and pAQP2 protein in GD rats. In conclusion, enhanced protein abundance of Na+ transporters and Na+ channels with Na+ retention occurred with GD. OPC-31260 reversed upregulation and apical trafficking of AQP2 and pAQP2 in association with improved urinary diluting capacity and increased water excretion after oral water loading.

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).

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.

Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality

2005 ◽  
Vol 288 (5) ◽  
pp. F912-F920 ◽  
Author(s):  
Yuqiang Ge ◽  
Dowahn Ahn ◽  
Peter K. Stricklett ◽  
Alisa K. Hughes ◽  
Masashi Yanagisawa ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Urine Volume ◽  
Urine Osmolality ◽  
Water Metabolism ◽  
Urinary Osmolality ◽  
Water Load ◽  
Endothelin 1 ◽  
Normal Water

In vitro studies suggest that endothelin-1 (ET-1) inhibits vasopressin (AVP)-stimulated water permeability in the collecting duct (CD). To evaluate the role of CD-derived ET-1 in regulating renal water metabolism, the ET-1 gene was selectively disrupted in the CD (CD ET-1 KO). During normal water intake, urinary osmolality (Uosm), plasma Na concentration, urine volume, and renal aquaporin-2 (AQP2) levels were unchanged, but plasma AVP concentration was reduced in CD ET-1 KO animals. CD ET-1 KO mice had impaired ability to excrete an acute, but not a chronic, water load, and this was associated with increased CD ET-1 mRNA in control, but not CD ET-1 KO, mice. In response to continuous infusion of 1-desamino-8-d-arginine vasopressin, CD ET-1 KO mice had greater increases in Uosm, V2 and AQP2 mRNA, and phosphorylation of AQP2. CD suspensions from CD ET-1 KO mice had enhanced AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ET-1 KO increases renal sensitivity to the urinary concentrating effects of AVP and suggest that ET-1 functions as a physiological autocrine regulator of AVP action in the CD.

Mechanism of cold diuresis in the rat

1983 ◽  
Vol 244 (2) ◽  
pp. F210-F216 ◽  
Author(s):  
M. L. Morgan ◽  
R. J. Anderson ◽  
M. A. Ellis ◽  
T. Berl
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Plasma Osmolality ◽  
Urine Osmolality ◽  
Urine Flow ◽  
Hemodynamic Parameters ◽  
Water Excretion ◽  
Urinary Osmolality ◽  
6 Hydroxydopamine ◽  
Renal Water Excretion

The effect of cold exposure (CE) on renal water excretion has not been clearly delineated. Conscious rats were exposed to decreased ambient temperature (15 degrees C). Forty-five minutes of CE resulted in reversible increases in urine flow and decreases in urine osmolality. The diuresis was not due to a diminished response to vasopressin (VP), as the antidiuresis associated with 500 microU of Pitressin given to water-diuresing rats was comparable at 15 and 30 degrees C. To determine whether the diuresis was due to intrarenal factors, glomerular filtration rate, renal blood flow, sodium excretion, and osmolar clearances were measured and found to be equivalent during control and cold conditions. To determine whether the observed diuresis was due to suppression of endogenous VP, VP-free Brattleboro rats undergoing a constant VP infusion were cold exposed. In these rats, CE was not associated with a change in either urine flow or urinary osmolality. This antidiuretic hormone-mediated mechanism was corroborated by a decrease in immunoassayable VP levels. To determine the mechanism whereby CE suppresses endogenous VP, plasma osmolality and hemodynamic parameters were measured. Although CE was not associated with a change in plasma osmolality, it did result in a significant increase in both mean arterial pressure and cardiac index. Pretreatment of rats with 6-hydroxydopamine prevented both the increase in mean arterial pressure and cold diuresis. We conclude that the diuresis observed upon exposure to 15 degrees C results from nonosmotic suppression of endogenous VP, as a consequence of the increase in mean arterial pressure.

The Effect of Papillectomy on Renal Function in the Rat during Hydropenia and after an Acute Saline Load

1972 ◽  
Vol 50 (7) ◽  
pp. 662-673 ◽  
Author(s):  
D. R. Wilson
Keyword(s):  
Renal Function ◽  
Partial Nephrectomy ◽  
Sodium Excretion ◽  
Free Water ◽  
Renal Medulla ◽  
Fractional Excretion ◽  
Urine Osmolality ◽  
Renal Handling ◽  
Water Excretion ◽  
Fractional Excretion Of Sodium

The effect of unilateral papillectomy on renal function in the rat was compared with the effect of partial nephrectomy which produced a similar decrease in glomerular filtration rate (G.F.R.) in the presence of an intact papilla. Under hydropenic conditions the kidney with papillectomy had a higher urine flow rate, sodium excretion rate, fractional sodium excretion, and osmolar clearance, while urine osmolality was lower. After an acute saline load the differences in sodium and water excretion disappeared, and fractional excretion of sodium and water were significantly higher in both types of kidney damage than in the contralateral control kidney. Free water reabsorption was lower in the papillectomized kidney after saline loading. Thus removal of the papilla resulted in abnormalities in the renal handling of salt and water which varied with the state of hydration of the animal and which were distinct from the effects of a reduction in G.F.R. by partial nephrectomy. It was concluded that the site of nephron loss, whether mainly in the renal medulla or in the cortex, may be another factor, in addition to G.F.R. and tubular reabsorption, which influences sodium and water excretion by the moderately damaged kidney.

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.

Urinary Concentration and Dilution after Unilateral Nephrectomy in the Rat

1975 ◽  
Vol 49 (6) ◽  
pp. 563-572
Author(s):  
D. S. Emmanouel ◽  
M. D. Lindheimer ◽  
A. I. Katz
Keyword(s):  
Antidiuretic Hormone ◽  
Free Water ◽  
Urine Osmolality ◽  
Renal Tissue ◽  
Unilateral Nephrectomy ◽  
Urinary Concentration ◽  
Sprague Dawley ◽  
Fluid Delivery ◽  
Sprague Dawley Rats ◽  
Water Formation

1. The effects of unilateral nephrectomy on urinary concentration and dilution were studied in Sprague—Dawley rats. To exclude incomplete suppression of antidiuretic hormone, free water formation was also studied in rats with congenital diabetes insipidus (Brattleboro strain). 2. Urinary solute-free water formation was similar in Sprague—Dawley and Brattleboro rats. Unineph-rectomized animals excreted a water load promptly and diluted their urine to the same degree as control rats. Maximal values for Cwater and TCwater per kidney were higher after nephrectomy, but were similar to those of control rats at comparable rates of fluid delivery to the distal nephron. Renal tissue osmolality was similar in uninephrectomized and sham-operated animals, indicating that non-antidiuretic hormone-dependent backflux of filtrate was the same in the two groups. The only defect observed in uninephrectomized animals was a small reduction in maximal urine osmolality. 3. These results demonstrate that free water formation and reabsorption are unaffected by unilateral nephrectomy and suggest that, in the remaining kidney, filtrate reabsorption along the entire nephron increases in proportion to the increment in glomerular filtration.

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