Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032617 (polyuria)
 3,056 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a patient with lithium-induced nephrogenic diabetes insipidus in whom detailed investigations of distal tubular function were performed. Clearance of free water during water diuresis was found to be augmented. This suggests proximal suppression of sodium reabsorption by lithium. Reabsorption of free water during high solute clearance was impaired. Acidification of the urine following ammonium chloride loading was abnormal, and this was corrected by sodium sulfate infusion. The cellular mechanism of lithium was investigated by means of indomethacin, an inhibitor of prostaglandin synthesis. Indomethacin caused a partial reversal of the nephrogenic diabetes insipidus, suggesting that the primary cellular action of lithium may be to inhibit the formation of cyclic AMP in the collecting duct cell, although a direct action of indomethacin in increasing solutes in the renal medulla could not be ruled out. It is possible that the lithium-induced polyuria is partially due to an enhancement by lithium of renal prostaglandin action.
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PMID:Lithium-induced nephrogenic diabetes insipidus: studies of tubular function and pathogenesis. 4 18

The diffusional and osmotic water permeability of collecting ducts in isolated papillae of rats' kidneys were measured in papillae taken from normal and lithium pretreated rats. The diffusional water permeability of collecting ducts in papillae from normal rats in the absence of ADH was 4.1 +/- 0.2 (S.E.M.) (n = 18) muM s-1 increasing to 7.2 +/- 0.6 mum s-1 with ADH. Values obtained with lithium (10 mM) in the medium, perfusate or both and in papillae taken from lithium pretreated rats did not differ significantly from the above. The cyclic AMP content of the papillae taken from normal rats was 83 +/- 6 pm mg protein in the absence of ADH and increased to 196 +/- 12 (n = 13) with 500 mu units ml-1 ADH. Lithium 10 mM in the medium did not alter this response. Papillae from lithium pretreated rats had a similar basal level of cyclic AMP but the increment in a lithium (10 mM) medium after ADH was significantly less. These results indicate that the impaired water handling of lithium treated rats is probably not due to a failure of the membrane to increase its permeability to water after ADH. Though lithium does alter the production of cyclic AMP this is not believed to be important regarding any alteration in water permeability. We believe it is probable that lithium interferes with sodium chloride transport at some more proximal nephron segment thereby producing the syndrome of polyuria.
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PMID:The effect of lithium on the permeability response induced in the collecting duct by antidiuretic hormone. 18 85

The antidiuretic and urinary cyclic AMP response to supramaximal vasopressin infusion was studied in normal rats and in rats with lithium-polyuria. The animals were anaesthetized and then infused with a solution designed to produce excessive water diuresis and to lower basal cyclic AMP excretion. In 6 control animals not infused with vasopressin (1) urinary cyclic AMP excretion decreased during the infusion period. Vasopressin infusion (300 muU/min.) consistantly induced antidiuresis in all of 13 control rats (II); but the urinary cyclic AMP response varied individually from a significant increase in 6 animals to either no change or to a decrease in the remaining animals. The antidiuretic response to vasopressin was inhibited by 85% in 10 animals with marked polyuria induced by lithium administration (III). None of the animals in this group showed a significant increase of cyclic AMP excretion in response to vasopressin. The average rate of cyclic AMP excretion, which was equal in the two groups before vasopressin, was signifimantly lower in group III than in group II during vasopressin infusion. It is suggested that the increase in cyclic AMP excretion during vasopressin antidiuresis, although not consistant, most likely reflects hormone-induced changes of intracellular cyclic AMP levels in the renal medulla. Thus, the data suggest that the nephrogenic diabetes insipidus syndrome produced by lithium is associated with a defect in the renal formation of cyclic AMP in response to vasopressin.
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PMID:Antidiuretic and urinary cyclic AMP response of vasopressin in normal rats and in rats with lithium-polyuria. 19 Aug 61

A 6-week-old girl with fever, hypernatraemia, dehydration, and polyuria failed to concentrate urine in response to exogenous vasopressin administration. There was no family history of nephrogenic diabetes insipidus. When she was 15 months old, the infusion of vasopressin did not produce an increase in urinary cyclic-AMP.
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PMID:Congenital nephrogenic diabetes insipidus in a baby girl. 21 90

Li inhibition of noradrenergic adenylate cyclase may be due to inhibition by Li of agonist-induced increases in GTP binding to G-protein. Such inhibition by Li of G-protein function could have effects on phosphatidyl-inositol-mediated second messenger systems as well as on cyclic AMP-mediated systems. However, Sherman, Berridge and others have proposed that Li affects phosphatidylinositol metabolism by inhibiting inositol-1-phosphatase. We recently have been able to measure inositol-1-phosphatase in human red blood cells. Preliminary data on patients treated with Li compared with controls suggests that the enzyme is indeed inhibited in vivo in patients undergoing Li treatment. However, a series of experiments in rats on addition of inositol to Li treatment did not find that inositol could reverse Li effects. Chronic oral high dose inositol does not reverse Li-induced polyuria (measured by polydipsia), Li-induced weight loss or Li-induced depression of exploratory behavior. These results suggest that Li inhibition of inositol-1-phosphatase indeed occurs in vivo. However, the physiological significance of inositol-1-phosphatase inhibition is not yet established.
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PMID:Role of inositol-1-phosphatase inhibition in the mechanism of action of lithium. 215 51

The physiological basis for the polyuria and polydipsia occurring in some manic-depressive patients treated with lithium salts was studied in vivo and in vitro. Three lithium-treated polyuric patients, in whom other causes of a concentrating defect were excluded, had abnormal urinary concentrating abilities after a standard water depreviation test. Two of these patients failed to respond to exogenous vasopressin (ADH) and one had a subnormal response. The abilities of these patients to excrete solute-free water (C(H2O)) was comparable to normal subjects during steady-state water diuresis, suggesting no gross abnormalities in sodium transport. However, each of these patients demonstrated abnormally low capacities to reabsorb solute-free water (T(C) (H2O)) under hydropenic conditions after administration of hypertonic saline and vasopressin. These in vivo findings demonstrate at least a nephrogenic basis for the diabetes insipidus syndrome manifested by these three patients. The defect in water transport was further characterized in toad urinary bladders in vitro. Short-circuit current (I) and water flow (W) were studied under basal, ADH-stimulated, and cyclic adenosine 3',5'-monophosphate (c-AMP)-stimulated conditions. Increasing mucosal [Li(+)] progressively inhibited basal I, and both I and W induced by ADH. Significant inhibition of basal and ADH-induced I was observed at mucosal [Li(+)] < 1.1 mEq/liter, and of ADH-induced W at mucosal [Li(+)] = 11 mEq/liter. On the other hand, at these lithium concentrations, neither c-AMP-stimulated W nor I was inhibited. Increasing serosal [Li(+)] produced significant inhibition of basal I only at [Li(+)] at least 50-fold greater than at the mucosal (urinary) surface. These in vitro studies confirm that mucosal lithium inhibits the action of ADH, but not c-AMP. Hence, lithium appears to be a significant inhibitor of ADH-stimulated water flow, probably acts from the urinary surface, and appears to exert its effect at a site biochemically proximal to c-AMP action.
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PMID:Lithium-induced nephrogenic diabetes insipidus: in vivo and in vitro studies. 434 1

The mechanism of lithium-induced diabetes insipidus was investigated in 96 patients and in a rat model. Polydipsia was reported by 40% and polyuria (more than 3 liter/day) by 12% of patients receiving lithium. Maximum concentrating ability after dehydration and vasopressin was markedly impaired in 10 polyuric patients and was reduced in 7 of 10 nonpolyuric patients studied before and during lithium therapy. Severe polyuria (more than 6 liter/day) was unresponsive to trials of vasopressin and chlorpropamide, but improved on chlorothiazide. Rats receiving lithium (3-4 meq/kg/day) developed massive polyuria that was resistant to vasopressin, in comparison to rats with comparable polyuria induced by drinking glucose. Analysis of renal tissue in rats with lithium polyuria showed progressive increase in the concentration of lithium from cortex to papilla with a 2.9-fold corticopapillary gradient for lithium. The normal corticopapillary gradient for sodium was not reduced by lithium treatment. The polyuria was not interrupted by brief intravenous doses of vasopressin (5-10 mU/kg) or dibutyryl cyclic AMP (10-15 mg/kg) capable of reversing water diuresis in normal and hypothalamic diabetes insipidus rats (Brattleboro strain). The present studies suggest that nephrogenic diabetes insipidus is a common finding after lithium treatment and results in part from interference with the mediation of vasopressin at a step distal to the formation of 3',5' cyclic AMP.
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PMID:On the mechanism of lithium-induced diabetes insipidus in man and the rat. 436 Aug 56

The effect of potassium depletion on urinary prostaglandin E and cyclic AMP excretion was studied in female Sprague-Dawley and in Brattleboro rats. The animals were fed a potassium-free diet for 20 days which resulted in an average decrease in serum potassium of 25% in both strains. In the Sprague-Dawley rats, potassium depletion increased urine volume from 5.5 +/- 0.9 ml/day to 25.9 +/- 3.5 ml/day (p less than 0.001), decreased urinary osmolality from 1483 +/- 87 mosmol/kg H2O to 372 +/- 12 mosmol/kg H2O (p less than 0.001) and suppressed urinary cyclic AMP excretion from 56.95 +/- 3.81 nmoles/day to 0.83 +/- 0.40 nmoles/day (p less than 0.001). Potassium depletion in the Brattleboro rats did not affect these parameters. Excretion of prostaglandin E-like immunoreactivity in urine did not change in either strain with potassium depletion. The findings support the hypothesis that prostaglandins do not play a significant role in the polyuria caused by potassium deficiency in rats. Hypokalemia may cause polyuria by suppression of vasopressin-sensitive cyclic AMP generation, leading to a decrease in water permeability.
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PMID:The role of urinary prostaglandin E and cyclic AMP in the polyuria of hypokalemia in rats. 624 32

The hydro-osmotic response of the toad bladder to antidiuretic hormone and cyclic AMP was inhibited by the methoxyflurane metabolite, fluoride. The osmotic transfer of water in the absence of hormone was unaffected by fluoride as was the hydroosmotic response due to hypertonicity of the serosal bathing media. Osmotic water movements across N-ethylmaleimide-"fixed" vasopressin or cyclic AMP-stimulated bladders were likewise unchanged by fluoride, suggesting that fluoride is exerting an action subsequent to the endogenous formation of cyclic AMP but before the final effector mechanism. Fluoride increased intracellular cyclic AMP concentrations even in the presence of added hormone. Fluoride suppressed calmodulin activity and prevented its activation of phosphodiesterase. Fluoride had no effect on oxygen consumption of toad urinary bladder cells but reduced lactate formation and anerobic metabolism. This decrease in the glycolytic energy source did not contribute to the inhibition of the hormonal response since 2-deoxyglucose was without effect on hormonal mediated osmotic-water flow. It is postulated that the fluoride-induced polyuria after methoxyflurane anesthesia may be due in part to the ability of fluoride to interfere with calcium and calmodulin-initiated processes (other than phosphodiesterase activity) that may occur in the stimulus-reabsorption coupling response of antidiuretic hormone.
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PMID:Fluoride inhibition of the hydro-osmotic response of the toad urinary bladder to antidiuretic hormone. 627 Mar 9

Administration of sodium fluoride results in vasopressin-resistant polyuric "renal failure" resembling nephrogenic diabetes insipidus. However, the renal tubular site of action of fluoride is not clear. Fischer 344 rats received acute i.v. infusions of sodium fluoride (0.3, 1.47 and 2.20 mumol/min/kg b.wt.) for 2.5 hr which resulted in dissipation of the renal medullary tissue osmotic gradient and a sustained, dose-related increase in fractional sodium excretion and urine flow. In additional experiments, free water reabsorption and excretion were decreased by fluoride, but the decrease in free water excretion occurred only when the fluoride-induced polyuria preceded the onset of the water diuresis. Slices of renal medulla from fluoride-treated rats had lower cyclic AMP concentrations than did slices from control rats and the responsiveness of the medullary tissue to vasopressin was markedly reduced. These data indicate that the fluoride ion dissipates the concentration gradient in the renal medulla largely by inhibiting NaCl reabsorption in the ascending limb of Henle's loop and inhibits antidiuretic hormone-mediated water reabsorption across the collecting duct.
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PMID:Renal tubular effects of sodium fluoride. 629 Jun 33


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