Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two pregnant women developed overt polyuria (up to 11 l/day) and polydipsia during their second and third trimesters of pregnancy. In one patient hydronephrosis was present. Both patients suffered from mild gestational diabetes mellitus. Plasma sodium was 145 and 162 mmol/l. Polyuria and urinary hypo-osmolality responded well to desmopressin acetate. After delivery, polyuria and polydipsia disappeared in one patient and significantly improved in the other. Infusion of hypertonic saline one and two weeks respectively after delivery led to plasma hyper-osmolality (294 mosmol/kg and 305 mosmol/kg) without detectable stimulation of arginine vasopressin (AVP). Anterior pituitary function was normal. No stimulation of AVP occurred following insulin-induced hypoglycemia. AVP plasma disappearance after i.v. pulse injection of 1 microgram AVP as well as AVP plasma concentration after continuous infusion of 10 ng AVP/min was studied two weeks after delivery in one patient. The results suggested markedly elevated degradation of AVP compared to control subjects, probably due to an increased vasopressin activity. Eight months after delivery, hypertonic saline infusion in one patient led to a plasma-osmolality of 312 mosmol/kg without stimulation of AVP. In the second patient, AVP was not detectable (less than 0.2 pg/ml) six months after delivery when plasma osmolality was 290 mosmol/kg. Our studies demonstrate that a subclinical compensated diabetes insipidus was preexistent in both patients. Exacerbation occurred due to an increased AVP-clearance and presumably due to the hemodynamic and hormonal alterations during pregnancy, including a mild gestational diabetes mellitus.
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PMID:[Transient polyuria in pregnancy in diabetes insipidus and gestational diabetes]. 177 Sep 4

Nitrofen and ethylenethiourea (ETU), agents known to prenatally induce hydronephrosis in rats, were assessed for their effects on postnatal renal functional maturation. Both were given by gavage to pregnant Sprague-Dawley rats on Gestation Day 11. Nitrofen was given at concentrations of 50 or 100 mg/kg, and ETU at 20, 40, or 60 mg/kg. Renal function was examined in the offspring from birth until after weaning, the period of renal functional maturation in the rat. Maximal urine concentrating ability was measured after DDAVP (desmopressin acetate, a vasopressin analog) challenge or water deprivation. Proximal tubule transport was measured in renal cortical slices. Various urinary parameters were measured. Both prenatal nitrofen and ETU exposure caused a large number of neonatal deaths at the high dose, and hydronephrosis was observed. The severity of the lesion increased with age. Hydronephrotic animals were deficient in urine concentrating ability, which became more pronounced after weaning. A few other urinary parameters were altered, but cortical function appeared to be unaffected. Rats prenatally exposed to nitrofen, but with apparently normal kidneys, were significantly compromised in their ability to produce a concentrated urine in response to DDAVP challenge, on Postnatal Days (PDs) 6 and 14. By PD 30, they were not different from controls in urine concentrating response. Rats prenatally exposed to the higher doses of ETU, but with grossly normal kidneys, had significantly decreased plasma clearances of certain electrolytes early in life, but by PD 27, they were not different from controls. Proximal tubule transport of PAH was increased on PD 7 in ETU-exposed pups, but this effect did not persist.
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PMID:Functional teratogens of the rat kidney. II. Nitrofen and ethylenethiourea. 322 Feb 15

The separate and combined effects of prenatal protein deficiency (6% casein) and prenatal nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) exposure (12.5 mg/kg on gestational d 7-21) on renal morphology in the 21-d fetal and postnatal rat were examined. Body weights and kidney weights were reduced in prenatally protein-deprived (PPD) pups at birth and on postnatal day (PND) 10. Numbers of mature glomeruli, creatinine clearance, water diuresis, and response of antidiuretic hormone (ADH), but not the concentrating ability, were lower in the PPD neonates. These changes suggest that prenatal protein deficiency delays renal development and possibly results in a decrease in glomerular clearance and in tubular response to a water load and to antidiuretic hormone. Prenatal nitrofen exposure reduced body weight and kidney size on PND 0 and 10. An increased incidence of hydronephrosis was indicated in the nitrofen-exposed fetus. Prenatal nitrofen exposure depressed the ability to excrete excess water, the response to ADH, and urine-concentrating ability. The functional deficits indicate tubular dysfunction, but little or no effect on glomerular function, as indicated by the absence of an effect on creatinine clearance. Postnatal survival was reduced to 22% by PND in the PPD plus nitrofen pups. Also, prenatal nitrofen exposure increased the susceptibility of the glomeruli in the gestational day (GD) 21 PPD fetus to the adverse effects of prenatal protein deficiency. By PND 10 the toxic effects were of the same order. Renal dysfunction may contribute to the increased mortality in PPD plus nitrofen pups by reducing the ability to respond to stress, but the effects are not sufficiently marked to be considered the primary cause of death.
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PMID:Kidney morphology and function in the young of rats malnourished and exposed to nitrofen during pregnancy. 374 36

The systemic and renal effects of high partial ureteral obstruction were investigated in a new model of experimental hydronephrosis. The test group comprised 12 contralaterally nephrectomized growing male New Zealand rabbits. As compared to the pyelographic findings in 6 unilaterally nephrectomized control animals, the test group could be divided into partially obstructed but non-hydronephrotic and obstructed-hydronephrotic subgroups. Animals of all 3 groups were capable of increasing their weight during the first 2 postoperative months. The mean plasma creatinine concentration remained normal in the obstructed group and even hydronephrosis was compatible with a normal serum creatinine level. As studied during forced hypotonic expansion, the renal response to a vasopressin analogue was significantly different in all 3 animal groups. Reciprocal but less marked differences were noted in the animals' ability to retain water during this test. We conclude that in this experimental model the magnitude of the antidiuretic response is inversely related to the radiologically defined degree of obstruction.
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PMID:The growing rabbit with a solitary, partially-obstructed kidney. Analysis of an experimental model with reference to the renal concentrating ability. 398 30

We have used homologous recombination to disrupt the mouse gene coding for the NaK2Cl cotransporter (NKCC2) expressed in kidney epithelial cells of the thick ascending limb and macula densa. This gene is one of several that when mutated causes Bartter's syndrome in humans, a syndrome characterized by severe polyuria and electrolyte imbalance. Homozygous NKCC2-/- pups were born in expected numbers and appeared normal. However, by day 1 they showed signs of extracellular volume depletion (hematocrit 51%; wild type 37%). They subsequently failed to thrive. By day 7, they were small and markedly dehydrated and exhibited renal insufficiency, high plasma potassium, metabolic acidosis, hydronephrosis of varying severity, and high plasma renin concentrations. None survived to weaning. Treatment of -/- pups with indomethacin from day 1 prevented growth retardation and 10% treated for 3 weeks survived, although as adults they exhibited severe polyuria (10 ml/day), extreme hydronephrosis, low plasma potassium, high blood pH, hypercalciuria, and proteinuria. Wild-type mice treated with furosemide, an inhibitor of NaK2Cl cotransporters, have a phenotype similar to the indomethacin-rescued -/- adults except that hydronephrosis was mild. The polyuria, hypercalciuria, and proteinuria of the -/- adults and furosemide-treated wild-type mice were unresponsive to inhibitors of the renin angiotensin system, vasopressin, and further indomethacin. Thus absence of NKCC2 in the mouse causes polyuria that is not compensated elsewhere in the nephron. The NKCC2 mutant animals should be valuable for uncovering new pathophysiologic and therapeutic aspects of genetic disturbances in water and electrolyte recovery by the kidney.
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PMID:Uncompensated polyuria in a mouse model of Bartter's syndrome. 1077 55

A 68-year-old man with a history of nephrectomy of the right kidney was admitted to our hospital with a 1-month history of polyuria (> 41 per day). He also exhibited hyposthenuria, which was unresponsive to treatment with exogenous vasopressin. Radiographic examination revealed partial obstruction of the left ureter and moderate hydronephrosis. The cause of the obstruction was cancer of the ureter. After drainage using a nephrostomy tube, the polyuria and hyposthenuria were gradually resolved. This is the first known case of nephrogenic diabetes insipidus due to hydronephrosis in a patient with a solitary kidney.
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PMID:Nephrogenic diabetes insipidus due to hydronephrosis in a patient with a solitary kidney. 1458 22

We describe a case of a novel mutant vasopressin 2 receptor (V2R)-dependent nephrogenic diabetes insipidus (NDI) with bilateral non-obstructive hydronephrosis in a middle aged man. This could be distinguished from aquaporin 2 (AQP2)-dependent NDI by the response of factor VIII and von Willebrand factor (vWF) to 1-deamino-8-D-arginine vasopressin (DDAVP) administration. A 47-year-old man was admitted to hospital because of polyuria, which had been present from infancy and was suspected of causing non-obstructive hydronephrosis. His mother's father, the older brother of his mother and his second daughter also all had polyuria. Sodium concentration, osmolality and vasopressin in blood were high, while sodium concentration and osmolality in urine were low. There were no changes in urine osmolality, factor VIII and vWF in response to DDAVP infusion. Neither was heart rate, diastolic blood pressure nor facial flushing affected. These findings suggested this case was V2R-dependent NDI rather than AQP2-dependent NDI. Molecular genetic analysis demonstrated that the patient had a V2R missense mutation involving a substitution of cysteine for arginine at position 104 (R104C) located in the first extracellular loop of the V2R. It was also found that the patient's mother and his second daughter were heterozygous for this R104C mutation.
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PMID:A case of a novel mutant vasopressin receptor-dependent nephrogenic diabetes insipidus with bilateral non-obstructive hydronephrosis in a middle aged man: differentiation from aquaporin-dependent nephrogenic diabetes insipidus by response of factor VII and von Willebrand factor to 1-diamino-8-arginine vasopressin administration. 1470 55

OREBP (osmotic response element-binding protein), also called TonEBP or NFAT5, is thought to induce the expression of genes that increase the accumulation of organic osmolytes to protect cells against a hypertonic environment. To investigate the consequences of lacking OREBP activity, transgenic (Tg) mice that overexpress OREBPdn (dominant negative form of OREBP) specifically in the epithelial cells of the renal collecting tubules were generated. These mice showed impairment in their urine concentrating mechanism, most likely due to reduced expression of the aquaporin AQP2 and the urea transporter UT-A1 and UT-A2 mRNAs. When deprived of water or after the administration of a vasopressin analogue, urine osmolality of the Tg mice was significantly increased but not to the same extent as that of the wild type mice. The expression of AQP2 and UT-A1, but not UT-A2 mRNAs, was increased to the same level as that of the wild type mice in the water deprivation state, indicating that the vasopressin regulatory mechanism was not affected by OREBPdn. These data indicate that in addition to vasopressin, OREBP is another essential regulator of the urine concentrating mechanism. Furthermore, the OREBPdn Tg mice developed progressive hydronephrosis soon after weaning, confirming the osmoprotective function of OREBP implicated by the in vitro experiments.
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PMID:Osmotic response element-binding protein (OREBP) is an essential regulator of the urine concentrating mechanism. 1534 63

We describe a novel missense mutant of arginine vasopressin (AVP)-dependent neurohypophyseal diabetes insipidus in an autosomal dominant family. A 54-year-old woman was admitted to our hospital because of thyroidectomy for thyroid cancer. After thyroidectomy she was found to have hypernatremia and polyuria and polydipsia both of which had been present from childhood. She had no obstructive hydronephrosis. Her father, father's younger sister and her third son also had polyuria and polydipsia. Basal plasma AVP concentration at normal plasma osmolality was normal but did not respond to increased plasma osmolality despite hyperosmolality during infusion of hypertonic saline infusion, indicating that plasma AVP secretion was impaired. Sodium concentration in urine and urine osmolality were low and increased after nasal administration of DDAVP. There was a diminished but bright signal of pituitary posterior gland on magnetic resonance T1 weighted image. Molecular genetic analysis demonstrated that the patient and her son had a single heterozygous missense mutation (G-->A) at nucleotide 1829 in 1 AVP allele, yielding an abnormal AVP precursor with lacking Glu-47 in its neurophysin II moiety. The abnormal AVP precursor may be related to the impaired AVP secretion.
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PMID:Novel mutant vasopressin-neurophysin II gene associated with familial neurohypophyseal diabetes insipidus. 1564 73

Congenital progressive hydronephrosis (cph) is a spontaneous recessive mutation that causes severe hydronephrosis and obstructive nephropathy in affected mice. The mutation has been mapped to the distal end of mouse chromosome 15, but the mutated gene has not been found. Here, we describe the identification of a single base pair change in aquaporin-2 (Aqp2) in cph mutants through genetic linkage mapping. The C-T change led to the substitution of a Ser (S256) by a Leu in the cytoplasmic tail of the Aqp2 protein, preventing its phosphorylation at S256 and the subsequent accumulation of Aqp2 on the apical membrane of the collecting duct principal cells. The interference with normal trafficking of Aqp2 by this mutation resulted in a severe urine concentration defect. cph homozygotes demonstrated polydipsia and produced a copious amount of hypotonic urine. The urine concentration defect could not be corrected by [deamino-Cys1,D-Arg8]-vasopressin (DDAVP, a vasopressin analog), characteristic of nephrogenic diabetes insipidus. The nephrogenic diabetes insipidus symptoms and the absence of developmental defects in the pyeloureteral peristaltic machinery in the mutants before the onset of hydronephrosis suggest that the congenital obstructive nephropathy is most likely a result of the polyuria. This study has revealed the genetic basis for the classical cph mutation and has provided direct genetic evidence that S256 in Aqp2 is indispensable for the apical accumulation, but not the general glycosylation or membrane association, of Aqp2.
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PMID:Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation. 1664 Oct 94


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