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)

Monosymptomatic nocturnal enuresis (MNE) in children is partly the result of inadequate reduction in the rate of urine output at night. This nocturnal polyuria is due to the lack of a rise in the anti-diuretic hormone, arginine vasopressin (AVP), and can be reduced or eliminated by treatment with desmopressin at bedtime. Since there is a 1% incidence of MNE among adults, this study investigated the circadian pattern of solute and water balance in nine young adult enuretics before and during desmopressin therapy and compared the results with nine-age- and sex-matched, healthy controls. Before treatment, enuretics and controls had similar total fluid intake, urine output, urine osmolality, plasma osmolality, plasma total protein, mean arterial pressure and plasma AVP. The circadian pattern of fluid intake was also normal in enuretics. This abnormality could not be attributed to a deficiency of plasma AVP or an increase in solute excretion, since both variables were similar to controls. Rather, their nocturnal polyuria appeared to be due to a marked nocturnal reduction in renal sensitivity to the antidiuretic effect of vasopressin. In seven enuretics, restudied during treatment with desmopressin (10-30 micrograms o.d.), circadian urine output was normal and enuresis was absent. These results indicate that: (i) The circadian pattern of urine output in healthy adults is largely due to a nocturnal decrease in solute excretion rather than a rise in plasma AVP; (ii) The subset of adults with persistent MNE also have nocturnal polyuria as a result of insensitivity to the antidiuretic action of AVP; (iii) These defects can be corrected by treatment with desmopressin.
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PMID:Pathophysiology and treatment of enuresis in adults. 1057 90

Carbamazepine is chemically related to imipramine. It can reduce prostaglandin E2-like activity in inflammation. It caused overflow urinary incontinence, increased bladder capacity, sensitized renal tubules to antidiuretic hormone and leading to antidiuresis. This encouraged to use carbamazepine to treat primary enuresis. Twenty-six patients of either sex with a history of enuresis from birth were included in study. Their age ranged between 7 and 15 years (mean 9.3 years). They were assessed by history, physical examination, blood glucose, renal function tests, intravenous urogram and videocystourethrography. 30 days drug-free observation was performed to establish baseline voiding pattern. This was followed by two, 30 day treatment periods of either placebo or carbamazepine (200 mg) tablets, in a randomized, double-blind cross-over design. There was one week washout period between medications. The patients or their parents received calendar sheet to record wet and dry nights and offered subjective opinions concerning changes in sleep patterns, occurrence of nocturia and appearance of side-effects. A tablet was given to each patient before retiring. Those patients who showed no response to carbamazepine and placebo would be treated with 100 mg of indomethacin suppositories. The results show that of 26 patients 20 had 7 to 30 of 30 dry nights with carbamazepine, while 6 had 0 to 5 of 30 dry nights. The latter 6 patients reacted in the same manner with placebo, 4 of them showed better response with use of indomethacin. Six patients had 10 to 15 of 30 dry nights during placebo therapy and 20 had 0 to 6 of 30 dry nights. The mean number of dry nights was 3.92 +/- 5.22 with placebo and was 18.8 +/- 8.82 with carbamazepine. The difference in response to placebo and carbamazepine was statistically significant (p < 0.001). All the patients who responded sufficiently to indomethacin slept until the morning. No side effect was noticed with either treatment and repeated serum electrolytes and other laboratory tests were normal after treatment. It might be concluded that carbamazepine is useful for treatment of primary nocturnal enuresis.
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PMID:Carbamazepine to treat primary nocturnal enuresis: double-blind study. 1065 88

Primary nocturnal enuresis is common and has considerable psychological ramifications for children as they get older. It is a familial condition with complex inheritance patterns. The pathophysiology of the condition appears to be related to poor arousal from sleep, nocturia due to deficient vasopressin release in sleep and possibly a decrease in functional bladder capacity especially at night. The mainstay of treatment is the bed-wetting alarm. In recent years, desmopressin nasal spray has found a clinical niche as a short-term solution for children attending school camps or sleeping over at friends' houses and as treatment in the medium term for those unresponsive to treatment with a bed-wetting alarm. It may also be used as an adjunct to the use of the alarm. Treatment with imipramine is increasingly in disfavour because the relapse rate is unacceptably high and fatal overdose is a real possibility.
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PMID:Nocturnal enuresis: what is happening? 1072 98

Synthetic oxytocin and vasopressin agonists and antagonists have become important tools for research and were instrumental in the identification of the four known receptor subtypes, V1a, V2, V1b (V3) and oxytocin, of these peptide hormones. However, the relative lack of receptor selectivity, particularly of the antagonists, has limited their usefulness as experimental probes and their potential as therapeutic agents. We now present some findings from our continuing studies aimed at the design of more selective oxytocin and vasopressin agonists and antagonists and a structure-activity relationship update on our recently discovered novel hypotensive vasopressin peptides. Bioassays have been, and continue to be, of critical importance in leading to the discovery of the novel agonists, antagonists and hypotensive peptides reported here. This paper highlights three main aspects of these studies. (1) Replacement of the tyrosine2 and/or phenylalanine3 residues in the V2 agonist deamino,[Val4,D-Arg8]arginine-vasopressin (dVDAVP) by thienylalanine resulted in selective V2 agonists with strikingly high potencies. However, the peptide solutions were unstable and lost activity over time. These highly potent V2 agonists, which are devoid of vasopressor activity, are promising leads for improving drugs for treating diabetes insipidus, enuresis and coagulation disorders. (2) Diaminopropionic acid and diaminobutyric acid substitution at position-5 in oxytocin and in V1a antagonists yielded, respectively, the first specific antagonist for the oxytocin receptor, desGly-NH2,d(CH2)5[D-Trp2,Thr4,Dap5]OVT and the first specific antagonist for the vasopressin V1a receptor, d(CH2)5[Tyr(Me)2,Dab5]AVP. The availability of single receptor subtype-specific or selective antagonists will enhance our ability to delineate receptor functions. Utilising these new receptor specific probes, we were able to show that the uterotonic action of vasopressin is mediated principally by oxytocin and not by V1a receptors. (3) Replacement of the phenylalanine3 residue in the V1a/V2/oxytocin antagonist, d(CH2)5[D-Tyr(Et)2,Val4]AVP, with arginine3 yielded the novel, selective, hypotensive vasopressin peptide, d(CH2)5[D-Tyr(Et)2,Arg3,Val4]AVP (Peptide I). Bioassay characterisations of Peptide I show that its vasodepressor action is independent of the peripheral autonomic, bradykinin, nitric oxide and prostaglandin systems and is not mediated by the known classical oxytocin and vasopressin receptors. These findings suggest the existence of a new vasopressin receptor subtype that may be relevant to the vasodilating action of vasopressin in regional vascular beds. Iodinatable hypotensive peptides have been synthesised and could be developed as markers for the putative new receptor. Ongoing structure-activity relationship studies on Peptide I have led to more potent and selective hypotensive peptides for use as new research tools and as leads for the development of a new class of antihypertensive agents.
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PMID:Discovery and design of novel and selective vasopressin and oxytocin agonists and antagonists: the role of bioassays. 1079 2

Nocturnal polyuria is common in the elderly. In this condition the normal circadian rhythm of urine production is reversed so that urine flow is higher at night than during the day. Elderly men with nocturnal polyuria are commonly referred for prostate surgery, which, not surprisingly, fails to relieve their symptoms. Compared with controls, patients with nocturnal polyuria have higher nocturnal sodium excretion but not higher nocturnal free-water clearance. Similar results have been obtained in children with nocturnal enuresis. Use of vasopressin analogues to induce water retention in elderly patients with nocturnal polyuria is illogical and potentially hazardous; nocturia can be more safely alleviated by diuretic therapy. Nocturnal polyuria in the elderly is associated with hypertension: this is consistent with studies in younger age groups that show that essential hypertension is associated with nocturia and with increased night/day ratios for sodium excretion. We propose that nocturnal polyuria and essential hypertension share some of the same pathophysiological determinants. Specifically, we suggest that a defect in the nitric-oxide pathway may lead to resetting of the pressure-natriuresis relation in the kidney, sodium retention, and compensatory nocturnal natriuresis. This suggestion is consistent with evidence that ageing and essential hypertension are both associated with defects in the nitric-oxide pathway. Our hypothesis has obvious therapeutic implications. More generally, studying the pathogenesis of nocturnal polyuria in the elderly may advance our understanding of the pathogenesis of essential hypertension.
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PMID:Relation of nocturnal polyuria of the elderly to essential hypertension. 1084 Nov 44

This study examined the hypothesis that nocturnal enuresis might be paralleled by aquaporin 2 (AQP2) urinary excretion. Eighty children who experienced nocturnal enuresis were studied and compared with 9 healthy children. The 24-h urine samples were divided into two portions: night collections and day collections. Creatinine equivalents of urine samples from each patient were analyzed by Western blotting. AQP2 levels were semiquantified by densitometric scanning and reported as a ratio between the intensity of the signal in the day urine sample versus the night urine sample (D/N AQP2 ratio). The D/N AQP2 ratio was 0.59 +/- 0.11 (n = 9) in healthy children and increased to 1.27 +/- 0.24 (n = 10) in a subpopulation of enuretic children who had low nocturnal vasopressin levels. In enuretic children who displayed hypercalciuria and had normal vasopressin levels, the D/N AQP2 ratio was 1.05 +/- 0.27 (n = 8). These data indicate that reduced secretion of vasopressin and absorptive hypercalciuria are independently associated with an approximately twofold increase in the urinary D/N AQP2 ratio. When low nocturnal vasopressin levels were associated with hypercalciuria, a nearly threefold increase in the D/N AQP2 ratio was observed (1. 67 +/- 0.41, n = 11). In addition, in all enuretic patients tested, the urinary D/N AQP2 ratio correlates perfectly with the severity of the disorder (nocturnal polyuria). The findings reported in this article indicate that urinary AQP2 correlates with the severity of enuresis in children.
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PMID:Urinary aquaporin 2 and calciuria correlate with the severity of enuresis in children. 1100 18

OPC-51803 is the first nonpeptide vasopressin (AVP) V(2)-receptor-selective agonist. Its pharmacological profile, including antidiuretic action and receptor binding, was characterized using conscious Brattleboro rats with hereditary diabetes insipidus and Sprague-Dawley rats. In membrane preparations from the liver and kidney, OPC-51803 displaced the [(3)H]AVP binding to V(2)-receptors (K(i) = 49.8 +/- 8.1 nM) more greatly than that to V(1a)-receptors (K(i) = 1061 +/- 60 nM), showing a 21 times higher affinity for V(2)-receptors. At single oral doses of 0.003 to 0.3 mg/kg in female Brattleboro rats, OPC-51803 decreased urine volume (from 10.8 +/- 1.1 to 0.5 +/- 0.2 ml during 0-2 h postdosing) and increased urinary osmolality (from 114 +/- 9 to 432 +/- 114 mOsm/kg) in a dose-dependent manner. During the period of 4-week treatment with OPC-51803, significant and constant antidiuresis was observed. In male Sprague-Dawley rats with normal plasma AVP levels, OPC-51803 at 0.03 to 0.3 mg/kg also produced a dose-dependent antidiuretic action (urine volume: from 2.6 +/- 0.6 to 1.1 +/- 0.2 ml at 0-4 h postdosing). Few changes in urinary parameters, serum parameters, or plasma hormone levels were observed. OPC-51803 did not change blood pressure or heart rate, or inhibit AVP-induced pressor response even at 30 mg/kg p.o. These results demonstrate that OPC-51803 is a V(2)-selective agonist that produces a significant antidiuretic action after single and multiple oral dosing in AVP-deficient and normal AVP states. The data suggest that OPC-51803 is a useful therapeutic drug in the treatment of hypothalamic diabetes insipidus, nocturnal enuresis, and some kinds of urinary incontinence.
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PMID:Antidiuretic effects of a nonpeptide vasopressin V(2)-receptor agonist, OPC-51803, administered orally to rats. 1108 35

Childhood nocturnal enuresis has traditionally been regarded as a multifaceted problem with a variety of treatment interventions. This paper proposes a model based on the notion that nocturnal enuresis arises through the ill functioning of one or more of the following three systems - a lack of vasopressin release during sleep; bladder instability; and/or an inability to arouse from sleep to bladder sensations. Clinical signs of each system are outlined and the appropriate treatment intervention for each is discussed. It is argued that addressing nocturnal enuresis in this way will enhance overall treatment effectiveness.
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PMID:The three systems: a conceptual way of understanding nocturnal enuresis. 1109 87

Nocturnal urinary continence is dependent on 3 factors: 1) nocturnal urine production, 2) nocturnal bladder function and 3) sleep and arousal mechanisms. Any child will suffer from nocturnal enuresis if more urine is produced than can be contained in the bladder or if the detrusor is hyperactive, provided that he or she is not awakened by the imminent bladder contraction. Urine production is regulated by fluid intake and several interrelated renal, hormonal and neural factors, foremost of which are vasopressin, renin, angiotensin and the sympathetic nervous system. Detrusor function is governed by the autonomic nervous system which under ideal conditions is under central nervous control. Arousal from sleep is dependent on the reticular activating system, a diffuse neural network that translates sensory input into arousal stimuli via brain stem noradrenergic neurons. Disturbances in nocturnal urine production, bladder function and arousal mechanisms have all been firmly implicated as pathogenetic factors in nocturnal enuresis. The group of enuretic children are, however, pathogenetically heterogeneous, and two main types can be discerned: 1) Diuresis-dependent enuresis - these children void because of excessive nocturnal urine production and impaired arousal mechanisms. 2) Detrusor-dependent enuresis - these children void because of nocturnal detrusor hyperactivity and impaired arousal mechanisms. The main clinical difference between the two groups is that desmopressin is usually effective in the former but not in the latter. There are two first-line therapies in nocturnal enuresis: the enuresis alarm and desmopressin medication. Promising second-line treatments include anticholinergic drugs, urotherapy and treatment of occult constipation.
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PMID:Enuresis--background and treatment. 1119 46

Desmopressin, a synthetic analogue of the antidiuretic hormone, is an effective medication for primary nocturnal enuresis for both children and adults. Its safety is well established. Although it has a favorable side effect profile, because of its pharmacological effect, intranasal desmopressin can rarely induce water intoxication with profound hyponatremia if given without adequate restriction of water intake. The authors describe an adult patient with water intoxication and severe hyponatremia accompanied by loss of consciousness and seizures after 2-day intranasal administration of desmopressin. The present and the previously reported cases emphasize the need for greater awareness of the development of this serious and potentiallyfatal complication. In addition, to adjust the drug to the lowest required dosage, adequate restriction of water intake is recommended, and serum levels of sodium should be measured periodically to allow for early detection of water intoxication and hyponatremia.
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PMID:Coma and seizures due to severe hyponatremia and water intoxication in an adult with intranasal desmopressin therapy for nocturnal enuresis. 1136 Oct 55


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