The Effect of Vasopressin on the Reabsorption of Sodium, Potassium and Urea by the Renal Tubules in Man

1970 ◽  
Vol 39 (4) ◽  
pp. 517-527 ◽  
Author(s):  
M. A. Barraclough ◽  
N. F. Jones
Keyword(s):  
Diabetes Insipidus ◽  
Collecting Duct ◽  
Normal Subjects ◽  
Solute Concentration ◽  
Tubular Reabsorption ◽  
Urinary Concentration ◽  
Renal Tubules ◽  
Confidence Limits ◽  
Patients With Diabetes ◽  
Sodium And Potassium

1. Changes in the urinary concentrations or urine/plasma (U/P) ratios of creatinine, urea, sodium and potassium were determined during the transition from water diuresis to antidiuresis when normal subjects and patients with diabetes insipidus were given injections of vasopressin. 2. In confirmation of previous work, it was found that after vasopressin administration the urinary concentration or U/P ratio of urea rose to a lesser degree than that of creatinine, indicating an increase in the tubular reabsorption of urea. 3. The urinary concentration, or U/P ratio, of sodium also rose to a lesser degree than that of creatinine. Thus vasopressin also increases the tubular reabsorption of sodium. 4. In contrast, the urinary concentration or U/P ratio of potassium tended to rise more than that of creatinine, indicating a decrease in the net tubular reabsorption of potassium. 5. Quantitative changes in the tubular handling of these urinary solutes were assessed by calculating the ratio—solute concentration during antidiuresis/solute concentration during diuresis—and then expressing this as a percentage of the corresponding ratio for creatinine. In subjects on a normal or high sodium intake the values thus obtained were: urea 72% (99% confidence limits 65–81%); sodium 79% (99% confidence limits 68–92%) and potassium 119% (99% confidence limits 102–139%). 6. In salt depleted subjects the values for these ratios were: urea 63% (99% confidence limits 60–65%) and sodium 36% (99% confidence limits 33–40%). Vasopressin had no consistent effect on potassium reabsorption in salt depleted subjects. 7. The effects of vasopressin on normal subjects and on patients with diabetes insipidus were similar. 8. It is suggested that these effects of vasopressin on sodium and potassium handling by the kidney occur in the collecting duct.

Radioimmunoassay for arginine-vasopressin in cold ethanol extracts of plasma.

1983 ◽  
Vol 29 (5) ◽  
pp. 882-884 ◽  
Author(s):  
J Camps ◽  
A Martínez-Vea ◽  
R M Pérez-Ayuso ◽  
V Arroyo ◽  
J M Gaya ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Hormone Secretion ◽  
Normal Subjects ◽  
Good Reliability ◽  
Inappropriate Antidiuretic Hormone Secretion ◽  
Physiological Conditions ◽  
Antidiuretic Hormone Secretion ◽  
Patients With Diabetes ◽  
Ethanol Extracts

Abstract A radioimmunoassay for arginine-vasopressin in human plasma with use of a commercially available antibody was developed and evaluated. The hormone was extracted from plasma with cold 98% ethanol, which showed a significantly higher (p less than .001) and more precise recovery than with the acetone-ether procedure (65.3 +/- 3.7% vs 50.8 +/- 6.0%, respectively). The sensitivity was 0.31 pg per tube. Results for normal subjects in different physiological conditions and in patients with diabetes insipidus and inappropriate antidiuretic hormone secretion showed the good reliability of the method.

scholarly journals Lithium: a versatile tool for understanding renal physiology

2013 ◽  
Vol 304 (9) ◽  
pp. F1139-F1149 ◽  
Author(s):  
Bellamkonda K. Kishore ◽  
Carolyn M. Ecelbarger
Keyword(s):  
Diabetes Insipidus ◽  
Glycogen Synthase ◽  
Purinergic Signaling ◽  
Collecting Duct ◽  
Renal Physiology ◽  
Urinary Concentration ◽  
Paradigm Shifts ◽  
Molecular Physiology ◽  
Versatile Tool

By virtue of its unique interactions with kidney cells, lithium became an important research tool in renal physiology and pathophysiology. Investigators have uncovered the intricate relationships of lithium with the vasopressin and aldosterone systems, and the membrane channels or transporters regulated by them. While doing so, their work has also led to 1) questioning the role of adenylyl cyclase activity and prostaglandins in lithium-induced suppression of aquaporin-2 gene transcription; 2) unraveling the role of purinergic signaling in lithium-induced polyuria; and 3) highlighting the importance of the epithelial sodium channel (ENaC) in lithium-induced nephrogenic diabetes insipidus (NDI). Lithium-induced remodeling of the collecting duct has the potential to shed new light on collecting duct remodeling in disease conditions, such as diabetes insipidus. The finding that lithium inhibits glycogen synthase kinase-3β (GSK3β) has opened an avenue for studies on the role of GSK3β in urinary concentration, and GSK isoforms in renal development. Finally, proteomic and metabolomic profiling of the kidney and urine in rats treated with lithium is providing insights into how the kidney adapts its metabolism in conditions such as acquired NDI and the multifactorial nature of lithium-induced NDI. This review provides state-of-the-art knowledge of lithium as a versatile tool for understanding the molecular physiology of the kidney, and a comprehensive view of how this tool is challenging some of our long-standing concepts in renal physiology, often with paradigm shifts, and presenting paradoxical situations in renal pathophysiology. In addition, this review points to future directions in research where lithium can lead the renal community.

Inherited secondary nephrogenic diabetes insipidus: concentrating on humans

2013 ◽  
Vol 304 (8) ◽  
pp. F1037-F1042 ◽  
Author(s):  
D. Bockenhauer ◽  
D. G. Bichet
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Collecting Duct ◽  
Lithium Treatment ◽  
Water Channel ◽  
Underlying Mechanism ◽  
Bartter Syndrome ◽  
Experimental Models ◽  
Urinary Concentration ◽  
Apparent Mineralocorticoid Excess

The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.

scholarly journals Treating lithium-induced nephrogenic diabetes insipidus with a COX-2 inhibitor improves polyuria via upregulation of AQP2 and NKCC2

2008 ◽  
Vol 294 (4) ◽  
pp. F702-F709 ◽  
Author(s):  
Gheun-Ho Kim ◽  
Nak Won Choi ◽  
Ju-Young Jung ◽  
Ji-Hyun Song ◽  
Chang Hwa Lee ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Collecting Duct ◽  
Urine Osmolality ◽  
Urinary Concentration ◽  
Prostaglandin E ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cox 2

Prostaglandin E2 may antagonize vasopressin-stimulated salt absorption in the thick ascending limb and water absorption in the collecting duct. Blockade of prostaglandin E2 synthesis by nonsteroidal anti-inflammatory drugs (NSAIDs) enhances urinary concentration, and these agents have antidiuretic effects in patients with nephrogenic diabetes insipidus (NDI) of different etiologies. Because renal prostaglandins are derived largely from cyclooxygenase-2 (COX-2), we hypothesized that treatment of NDI with a COX-2 inhibitor may relieve polyuria through increased expression of Na-K-2Cl cotransporter type 2 (NKCC2) in the thick ascending limb and aquaporin-2 (AQP2) in the collecting duct. To test this hypothesis, semiquantitative immunoblotting and immunohistochemistry were carried out from the kidneys of lithium-induced NDI rats with and without COX-2 inhibition. After male Sprague-Dawley rats were fed an LiCl-containing rat diet for 3 wk, the rats were randomly divided into control and experimental groups. The COX-2 inhibitor DFU (40 mg·kg−1·day−1) was orally administered to the experimental rats for an additional week. Treatment with the COX-2 inhibitor significantly relieved polyuria and raised urine osmolality. Semiquantitative immunoblotting using whole-kidney homogenates revealed that COX-2 inhibition caused significant increases in the abundance of AQP2 and NKCC2. Immunohistochemistry for AQP2 and NKCC2 confirmed the effects of COX-2 inhibition in lithium-induced NDI rats. The upregulation of AQP2 and NKCC2 in response to the COX-2 inhibitor may underlie the therapeutic mechanisms by which NSAIDs enhance antidiuresis in patients with NDI.

Lack of intramembranous particle clusters in collecting ducts of mice with nephrogenic diabetes insipidus

1985 ◽  
Vol 249 (4) ◽  
pp. F582-F589 ◽  
Author(s):  
D. Brown ◽  
G. I. Shields ◽  
H. Valtin ◽  
J. F. Morris ◽  
L. Orci
Keyword(s):  
Diabetes Insipidus ◽  
Water Permeability ◽  
Collecting Duct ◽  
Freeze Fracture ◽  
Indirect Evidence ◽  
Urinary Concentration ◽  
Morphological Marker ◽  
Intramembranous Particle ◽  
Collecting Ducts ◽  
Freeze Fracture Electron Microscopy

We suggested previously, on the basis of indirect evidence, that in two strains of mice with nephrogenic defects of urinary concentration the deficiency arose from an inadequate rise in water permeability of the collecting duct system. In this study we tested the question further by assuming that the frequency of intramembranous particle (IMP) clusters seen by freeze-fracture can be used as a morphological marker of vasopressin-induced water permeability. Three genotypes of mice were studied: 1) DI +/+ Severe, with florid, vasopressin-resistant diabetes insipidus; 2) DI +/+ Nonsevere, with an intermediate deficiency of urinary concentration; and 3) normal, VII +/+ mice. In addition, we examined a group of DI +/+ Severe mice that had been injected with exogenous 1-desamino-8-D-arginine vasopressin (DDAVP) subcutaneously for 3 days. Since the results in this group did not differ from those in untreated DI +/+ Severe mice, all data for this genotype were combined. IMP clusters within luminal membranes of inner medullary collecting duct principal cells were quantified by freeze-fracture electron microscopy. Urinary osmolality and percentage of cells showing clusters were, respectively: 203 +/- 43 mosmol/kg H2O and 0% in DI +/+ Severe mice; 1,133 +/- 86 and 33 +/- 4 in DI +/+ Nonsevere mice; and 2,234 +/- 190 and 52 +/- 5 in VII +/+ animals. With the exception of one animal, there was no overlap of the data, which were significantly different from one another for each variable. We conclude that in DI +/+ Severe mice, both endogenous and exogenous vasopressin are unable to increase the water permeability of medullary collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Aquaporins in the Kidney: From Molecules to Medicine

2002 ◽  
Vol 82 (1) ◽  
pp. 205-244 ◽  
Author(s):  
Søren Nielsen ◽  
Jørgen Frøkiær ◽  
David Marples ◽  
Tae-Hwan Kwon ◽  
Peter Agre ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Water Balance ◽  
Diabetes Insipidus ◽  
Proximal Tubule ◽  
Water Retention ◽  
Collecting Duct ◽  
Apical Plasma Membrane ◽  
Urinary Concentration ◽  
Principal Cells ◽  
Intracellular Vesicles

The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.

scholarly journals Combination exposure of melamine and cyanuric acid is associated with polyuria and activation of NLRP3 inflammasome in rats

2018 ◽  
Vol 315 (2) ◽  
pp. F199-F210 ◽  
Author(s):  
Feifei Wang ◽  
Qiaojuan Liu ◽  
Lizi Jin ◽  
Shan Hu ◽  
Renfei Luo ◽  
...  
Keyword(s):  
Protein Expression ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Cyanuric Acid ◽  
Collecting Duct ◽  
Urinary Concentration ◽  
Inflammasome Activation ◽  
Renal Tubules ◽  
Mrna Levels

The molecular mechanisms of melamine-induced renal toxicity have not been fully understood. The purpose of the study aimed to investigate whether melamine and cyanuric acid induced NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in the kidney, which may contribute to abnormal water and sodium handling in a rat model. Wistar rats received melamine (Mel; 200 mg·kg body wt−1·day−1), cyanuric acid (CA; 200 mg·kg body wt−1·day−1), or Mel plus CA (Mel + CA; 100 mg·kg body wt−1·day−1, each) for 2 wk. Mel + CA caused damaged tubular epithelial structure and organelles, dilated tubular lumen, and inflammatory responses. Crystals were observed in urine and serum specimen, also in the lumen of dilated distal renal tubules. The combined ingestion of Mel and CA in rats caused a markedly impaired urinary concentration, which was associated with reduced protein expression of aquaporin (AQP)1, 2, and 3 in inner medulla and α-Na-K-ATPase and Na-K-2Cl transporters in cortex and outer medulla. Mel + CA treatment was associated with increased protein expression of CD3 and mRNA levels of CD68 and F4/80 as well as phosphorylation of NF-κB in the kidney. Mel + CA treatment increased protein and mRNA expression of NLRP3 inflammasome components apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, and IL-1β in the inner medulla of rats. NF-κB inhibitor Bay 11-7082 reduced IL-1β expression induced by Mel + CA and prevented downregulation of AQP2 in inner medullary collecting duct cell suspensions. In conclusion, Mel + CA treatment caused urinary-concentrating defects and reduced expression of renal AQPs and key sodium transporters, which is likely due to the inflammatory responses and activation of NLRP3 inflammasome induced by crystals formed in the kidney.

scholarly journals Disruption of prostaglandin E2 receptor EP4 impairs urinary concentration via decreasing aquaporin 2 in renal collecting ducts

2015 ◽  
Vol 112 (27) ◽  
pp. 8397-8402 ◽  
Author(s):  
Min Gao ◽  
Rong Cao ◽  
Shengnan Du ◽  
Xiao Jia ◽  
Senfeng Zheng ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Diabetes Insipidus ◽  
Therapeutic Target ◽  
Collecting Duct ◽  
Urinary Concentration ◽  
Membrane Targeting ◽  
Dependent Manner ◽  
Potential Therapeutic Target ◽  
Aquaporin 2 ◽  
Collecting Ducts

The antidiuretic hormone arginine vasopressin is a systemic effector in urinary concentration. However, increasing evidence suggests that other locally produced factors may also play an important role in the regulation of water reabsorption in renal collecting ducts. Recently, prostaglandin E2 (PGE2) receptor EP4 has emerged as a potential therapeutic target for the treatment of nephrogenic diabetes insipidus, but the underlying mechanism is unknown. To evaluate the role of EP4 in regulating water homeostasis, mice with renal tubule-specific knockout of EP4 (Ksp-EP4−/−) and collecting duct-specific knockout of EP4 (AQP2-EP4−/−) were generated using the Cre-loxP recombination system. Urine concentrating defect was observed in both Ksp-EP4−/− and AQP2-EP4−/− mice. Decreased aquaporin 2 (AQP2) abundance and apical membrane targeting in renal collecting ducts were evident in Ksp-EP4−/− mice. In vitro studies demonstrated that AQP2 mRNA and protein levels were significantly up-regulated in mouse primary inner medullary collecting duct (IMCD) cells after pharmacological activation or adenovirus-mediated overexpression of EP4 in a cAMP/cAMP-response element binding protein-dependent manner. In addition, EP4 activation or overexpression also increased AQP2 membrane accumulation in a mouse IMCD cell line (IMCD3) stably transfected with the AQP2 gene, mainly through the cAMP/protein kinase A and extracellular signal-regulated kinase pathways. In summary, the EP4 receptor in renal collecting ducts plays an important role in regulating urinary concentration under physiological conditions. The ability of EP4 to promote AQP2 membrane targeting and increase AQP2 abundance makes it a potential therapeutic target for the treatment of clinical disorders including acquired and congenital diabetes insipidus.

DER INSULINHYPOGLYKÄMIE-TEST ALS FUNKTIONSPRÜFUNG DES HYPOTHALAMUS-HYPOPHYSEN-NEBENNIERENRINDEN-SYSTEMS.

1967 ◽  
Vol 54 (4) ◽  
pp. 681-695 ◽  
Author(s):  
H. Bethge ◽  
K. Irmscher ◽  
H. G. Solbach ◽  
W. Winkelmann ◽  
H. Zimmermann ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Clinical Signs ◽  
Normal Subjects ◽  
Normal Function ◽  
Adrenal Axis ◽  
Patients With Diabetes ◽  
Alimentary Obesity ◽  
Bilateral Adrenal Hyperplasia ◽  
Corticosteroid Response ◽  
Pituitary Adrenal Axis

ABSTRACT In 50 patients determinations of blood sugar and corticosteroids in plasma (11-OHCS) were carried out during insulin-induced hypoglycaemia. In 9 out of 11 patients with Cushing's syndrome (bilateral adrenal hyperplasia) the characteristic finding was a missing increase of 11-OHCS concentrations during hypoglycaemia. On the contrary, 5 patients with alimentary obesity and clinical signs of hypercorticism showed a normal or even increased adrenocortical response. The results obtained in 7 patients with uncomplicated central diabetes insipidus did not differ from those in normal subjects, while 2 further patients with diabetes insipidus, complicated with secondary adrenocortical insufficiency, failed to respond. Findings in 12 patients with anorexia nervosa are consistent with a normal function of the hypothalamo-pituitary-adrenal axis. According to plasma corticosteroid response during hypoglycaemia results obtained in 15 patients with disorders of hypothalamus and/or hypophysis may be divided into three groups. The significance of this classification with regard to replacement therapy is discussed. Observations show that plasma corticosteroid estimations during insulin-induced hypoglycaemia provide a simple and reliable method to ascertain the function of the hypothalamo-pituitary-adrenal axis (insulinhypoglycaemiatest).

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