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.

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.

Vasopressin-dependent upregulation of aquaporin-2 gene expression in glucocorticoid-deficient rats

2000 ◽  
Vol 279 (3) ◽  
pp. F502-F508 ◽  
Author(s):  
Takako Saito ◽  
San-E Ishikawa ◽  
Fumiko Ando ◽  
Minori Higashiyama ◽  
Shoichiro Nagasaka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Load Test ◽  
Sprague Dawley ◽  
Water Excretion ◽  
Water Load ◽  
Aquaporin 2 ◽  
Sprague Dawley Rats ◽  
Glucocorticoid Deficiency ◽  
Aqp2 Gene ◽  
Impaired Water

We determined alterations in renal aquaporin-2 (AQP2) gene expression in association with impaired water excretion in glucocorticoid-deficient rats. After adrenalectomy, Sprague-Dawley rats were administered aldosterone alone by osmotic pumps (glucocorticoid-deficient rats). As a control, both aldosterone and dexamethasone were administered. These animals were subjected to the studies on days 7–14. The expressions of AQP2 mRNA and protein in kidney of the glucocorticoid-deficient rats were increased by 1.6- and 1.4-fold compared with the control rats, respectively. An acute oral water load test verified the marked impairment in water excretion in the glucocorticoid-deficient rats. One hour after the water load, the expressions of AQP2 mRNA and protein were significantly reduced in the control rats, but they remained unchanged in the glucocorticoid-deficient rats. However, there was no alteration in [3H]arginine vasopressin (AVP) receptor binding and AVP V2 receptor mRNA expression in the glucocorticoid-deficient rats. A V2-receptor antagonist abolished the increased expressions of AQP2 mRNA and protein in the glucocorticoid-deficient rats. These results indicate that augmented expression of AQP2 participates in impaired water excretion, dependent on AVP, in glucocorticoid deficiency.

The Influence of Indomethacin on Renal Concentrating and Diluting Capacity in Sickle Cell Nephropathy

1982 ◽  
Vol 63 (1) ◽  
pp. 53-58 ◽  
Author(s):  
P. E. de Jong ◽  
L. T. W. de Jong-Van Den Berg ◽  
D. de Zeeuw ◽  
A. J. M. Donker ◽  
H. Schouten ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Water Deprivation ◽  
Sickle Cell Anaemia ◽  
Distal Tubule ◽  
Control Group ◽  
Water Excretion ◽  
Urinary Osmolality ◽  
Water Loading ◽  
Renal Prostaglandins ◽  
Urea Reabsorption

1. The effects of indomethacin on water excretion during both vasopressin stimulation and inhibition were studied in control subjects and in patients with sickle cell anaemia. 2. In the control group as well as in the group of patients with sickle cell anaemia sodium and urea retention occurred after indomethacin in the water-depleted state. During water loading, indomethacin induced sodium retention without urea reabsorption. 3. In healthy volunteers indomethacin increased urinary osmolality during water deprivation, but not after water loading. In contrast, in patients with sickle cell anaemia indomethacin caused a rise in urinary osmolality during water loading, but not after water deprivation. 4. The findings support the view that indomethacin promotes solute reabsorption in the distal tubule. 5. From our observations we conclude that renal prostaglandins are not involved in the urinary concentrating defect of patients with sickle cell anaemia. On the other hand, the normal diluting capacity in sickle cell anaemia appears to depend on renal prostaglandins.

scholarly journals Dietary Tryptophan Supplementation Alters Fat and Glucose Metabolism in a Low-Birthweight Piglet Model

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2561
Author(s):  
Parniyan Goodarzi ◽  
Mohammad Habibi ◽  
Kennedy Roberts ◽  
Julia Sutton ◽  
Cedrick Ndhumba Shili ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Low Birthweight ◽  
Glucose Transporter ◽  
Protein Abundance ◽  
Metabolic Complications ◽  
Glucose And Lipid Metabolism ◽  
Glucose Transporter 2 ◽  
Lower Protein ◽  
Type 3

Low birthweight (LBW) is associated with metabolic complications, such as glucose and lipid metabolism disturbances in early life. The objective of this study was to assess: (1) the effect of dietary tryptophan (Trp) on glucose and fat metabolism in an LBW piglet model, and (2) the role peripheral 5-hydroxytryptamine type 3 (5HT3) receptors in regulating the feeding behavior in LBW piglets fed with Trp-supplemented diets. Seven-day-old piglets were assigned to 4 treatments: normal birthweight-0%Trp (NBW-T0), LBW-0%Trp (LBW-T0), LBW-0.4%Trp (LBW-T0.4), and LBW-0.8%Trp (LBW-T0.8) for 3 weeks. Compared to LBW-T0, the blood glucose was decreased in LBW-T0.8 at 60 min following the meal test, and the triglycerides were lower in LBW-T0.4 and LBW-T0.8. Relative to LBW-T0, LBW-T0.8 had a lower transcript and protein abundance of hepatic glucose transporter-2, a higher mRNA abundance of glucokinase, and a lower transcript of phosphoenolpyruvate carboxykinase. LBW-T0.4 tended to have a lower protein abundance of sodium-glucose co-transporter 1 in the jejunum. In comparison with LBW-T0, LBW-T0.4 and LBW-T0.8 had a lower transcript of hepatic acetyl-CoA carboxylase, and LBW-T0.4 had a higher transcript of 3-hydroxyacyl-CoA dehydrogenase. Blocking 5-HT3 receptors with ondansetron reduced the feed intake in all groups, with a transient effect on LBW-T0, but more persistent effect on LBW-T0.8 and NBW-T0. In conclusion, Trp supplementation reduced the hepatic lipogenesis and gluconeogenesis, but increased the glycolysis in LBW piglets. Peripheral serotonin is likely involved in the regulation of feeding behavior, particularly in LBW piglets fed diets supplemented with a higher dose of Trp.

The Relationship of Urinary Kallikrein Activity to Renal Salt and Water Excretion

1978 ◽  
Vol 54 (1) ◽  
pp. 39-45 ◽  
Author(s):  
S. B. Levy ◽  
R. P. Frigon ◽  
R. A. Stone
Keyword(s):  
Racial Differences ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Racial Groups ◽  
Urinary Kallikrein ◽  
Experimental Conditions ◽  
Water Excretion ◽  
Water Load ◽  
Black And White ◽  
Kallikrein Activity

1. We measured urinary kallikrein (kininogenin) excretion in black and white normotensive subjects during a variety of manipulations of salt and water balance. 2. A large intravenous saline load administered while the subjects were on an unrestricted sodium diet did not significantly change urinary kallikrein activity in either racial group. 3. After several days of dietary sodium restriction both racial groups increased their urinary kallikrein activity. An intravenous water load given then further increased urinary kallikrein activity. White subjects were studied for an additional 24 h period, and urinary kallikrein activity returned to pre-water load values, indicating that the excretion of a water load in sodium-depleted subjects is associated with an increase in kallikrein excretion. 4. Black subjects excreted less kallikrein in the urine than white subjects during the initial 24 h periods of unrestricted dietary sodium intake, but there were no other significant racial differences during the other experimental conditions.

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.

Plasma vasopressin and atrial natriuretic hormone levels in hypopituitarism with and without hydrocortisone treatments: responses to an acute water load

1992 ◽  
Vol 126 (3) ◽  
pp. 217-223 ◽  
Author(s):  
Tokihisa Kimura ◽  
Kozo Ota ◽  
Masaru Shoji ◽  
Minoru Inoue ◽  
Kazutoshi Sato ◽  
...  
Keyword(s):  
Arginine Vasopressin ◽  
Plasma Osmolality ◽  
Normal Subjects ◽  
Natriuretic Hormone ◽  
Water Load ◽  
Blood Volume Expansion ◽  
Atrial Natriuretic Hormone ◽  
Plasma Arginine ◽  
Glucocorticoid Deficiency ◽  
Atrial Natriuretic

To assess whether arginine vasopressin and atrial natriuretic hormone participate in impaired urinary dilution and excretion in glucocorticoid deficiency secondary to hypopituitarism. an acute oral water load of 20 ml·kg−1 BW was undertaken in the absence and presence of an oral hydrocortisone (60 mg) treatment in patients with ACTH deficiency (N= 7) and panhypopituitarism (N = 2). Plasma arginine vasopressin and atrial natriuretic hormone and renal water handling were simultaneously determined and compared with those in similarly water-loaded normal subjects. Plasma arginine vasopressin did not fall in response to decreased blood osmolality after an acute water load in the absence of hydrocortisone; plasma atrial natriuretic hormone did not change despite blood volume expansion; and impairment in urinary dilution and excretion remained. On the other hand, in the presence of hydrocortisone, plasma arginine vasopressin fell in response to a decrease in plasma osmolality and plasma atrial natriuretic hormone increased, thereby restoring urinary dilution and excretion. These results demonstrate that the impaired arginine vasopressin response to acute water loading play an essential role in deranged renal water and electrolyte handling in the state of glucocorticoid deficiency; the impaired release of atrial natriuretic hormone also may affect these disorders.

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.

The effect of Water Loading on urea metablism in Cattle

1971 ◽  
Vol 76 (3) ◽  
pp. 487-493
Author(s):  
J. E. Vercoe
Keyword(s):  
Urine Volume ◽  
Ammonia Level ◽  
Plasma Urea ◽  
Water Load ◽  
Urea Level ◽  
Water Loading ◽  
Urea Excretion ◽  
Effect Of Water ◽  
Low Nitrogen

SUMMARYSteers fed low nitrogen diets were infused intraruininally with water.Increasing the water load increased the urine volume and urinary urea excretion and depressed the plasma urea level.The effect of intraruminal water loading was studied in association with intravenous urea loading of 25 and 65 g N/day. When 25 g N/day as urea was infused intravenously, water loading did not significantly increase the urinary urea excretion but the plasma urea level was depressed. At 65 g N/day water loading increased the urinary urea excretion and decreased the plasma urea level.Significantly different relations between plasma urea and urea load existed for the ad lib. water and the water-loaded treatments but the relation between rumen ammonia level and plasma urea level was not affected by the water loading.The results are discussed with reference to the recycling of urea.

scholarly journals Is there a serum proteome signature to predict mortality in severe COVID-19 patients?

2021 ◽  
Author(s):  
Franziska Voellmy ◽  
Henk van den Toorn ◽  
Riccardo Zenezini Chiozzi ◽  
Ottavio Zucchetti ◽  
Albetto Papi ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Serum Proteins ◽  
Trypsin Inhibitors ◽  
Protein Abundance ◽  
Blood Samples ◽  
Serum Proteome ◽  
Serum Proteomics ◽  
Survivor Group ◽  
The Family ◽  
Type 3

Here we recorded serum proteome profiles of 33 COVID-19 patients admitted to respiratory and intensive care units because of respiratory failure. We received, for most patients, blood samples just after admission and at two more later timepoints. We focused on serum proteins different in abundance between the group of survivors and non-survivors and observed that a rather small panel of about a dozen proteins were significantly different in abundance between these two groups. The four structurally and functionally related type-3 cystatins AHSG, FETUB, HRG and KNG1 were all more abundant in the survivors. The family of inter-α-trypsin inhibitors, ITIH1, ITIH2, ITIH3 and ITIH4, were all found to be differentially abundant in between survivors and non-survivors, whereby ITIH1 and ITIH2 were more abundant in the survivor group and ITIH3 and ITIH4 more abundant in the non-survivors. ITIH1/ITIH2 and ITIH3/ITIH4 also did show opposite trends in protein abundance during disease progression. This panel of eight proteins, complemented with a few more, may represent a panel for mortality risk assessment and eventually even for treatment, by administration of exogenous proteins possibly aiding survival. Such administration is not unprecedented, as administration of exogenous inter-α-trypsin inhibitors is already used in the treatment of patients with severe sepsis and Kawasaki disease. The mortality risk panel defined here is in excellent agreement with findings in two recent COVID-19 serum proteomics studies on independent cohorts, supporting our findings. This panel may not be unique for COVID-19, as some of the proteins here annotated as mortality risk factors have previously been annotated as mortality markers in aging and in other diseases caused by different pathogens, including bacteria.

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