Vasopressin Abstracts 2

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Beta hypophamine (vasopressin), its effect upon intraocular pressure and aqueous flow in normal and glaucomatous eyes.
            (Becker and Christensen, 1956) Download
Introduction  The antidiuretic effect produced by the vasopressor hormone of the posterior pituitary lobe—β-hypophamine; vasopressin U. S. P.—is well known.1 It promotes the resorption of water by its action on the renal tubules.Interest in this hormonal effect was stimulated by a desire to increase the hemodilution following water drinking as a provocative test for glaucoma. It was hoped that the more intense and uncompensated decrease of osmotic pressure of the plasma produced by the administration of vasopressin with the water might lead to more consistent changes and a higher percentage of significant rises in intraocular pressure in glaucoma suspects. Meves2 reported that systemic Pituglandol (containing vasopressin and oxytocin) given with the water-provocative test produced a greater and more prolonged rise in ocular tension than could be obtained with water drinking alone. He also cited two patients with glaucoma who had negative water-provocative tests, but positive tests when

Daily patterns of secretion of neurohypophysial hormones in man: effect of age.
            (Forsling et al., 1998) Download
The neurohypophysial hormone vasopressin contributes to control of urine output and, while urine flow shows a clear daily rhythm, there has been debate as to whether this is true of neurohypophysial hormones. A study was performed on fifteen adult males, with a mean age of 25 years, over a 24 h period, nine blood samples being taken at regular intervals for the determination of neurohypophysial hormones and indices of fluid balance. Samples were taken via an indwelling cannula so that sleep was undisturbed. A daily variation in the plasma concentrations of oxytocin and vasopressin was demonstrated with concentrations reaching a nadir in the late afternoon. Concentrations of both hormones peaked at 02.00 h. Vasopressin concentrations were inversely correlated with packed cell volume, indicating that the altered hormone release was affecting fluid retention. Consistent with this was the observation that the relationship of plasma osmolality to vasopressin depended on the time of day. To determine the effect of ageing, a similar study was performed on nine healthy elderly subjects with a mean age of 70 years. The nocturnal peak of vasopressin was markedly attenuated, while oxytocin release was similar to that in the younger group. These observations confirm the existence of a daily rhythm in the plasma concentrations of neurohypophysial hormones and indicate that the amplitude of the vasopressin change decreases with age.

Effects of lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin on memory in healthy individuals and diabetes insipidus patients.
            (Laczi et al., 1982) Download
Central diabetes insipidus (DI) patients showed impairments in short- and long-term memory functions, but not in attention and concentration, as compared to healthy individuals. A single i.m. injection or sub-chronic intranasal administration of either lysine-vasopressin (LVP) or 1-deamino-8-D-arginine-vasopressin (DDAVP) normalized the disturbed memory functions in DI patients. These peptides also improved memory functions in healthy individuals.

Effects of desglycinamide-arginine-vasopressin (DG-AVP) on memory processes in diabetes insipidus patients and non-diabetic subjects.
            (Laczi et al., 1983) Download
The effects of desglycinamide9-arginine8-vasopressin (DG-AVP) on memory processes have been studied in patients with central diabetes insipidus (DI) and in non-diabetic control patients. Acute im injection of DG-AVP improved some aspects of short-term memory. Subchronic intranasal administration of DG-AVP facilitated short-term memory more consistently and in addition improved long-term memory. DG-AVP increased the attention, but only in the non-diabetic subjects. The effects of DG-AVP on memory processes persisted after discontinuation of treatment. DG-AVP did not affect the parameters for water and electrolyte metabolism, blood pressure and pulse rate neither in DI nor in the control patients. Thus, the memory effects of DG-AVP are probably mediated by a direct action on the central nervous system.

Effects of ginger on motion sickness and gastric slow-wave dysrhythmias induced by circular vection.
            (Lien et al., 2003)  Download
Ginger has long been used as an alternative medication to prevent motion sickness. The mechanism of its action, however, is unknown. We hypothesize that ginger ameliorates the nausea associated with motion sickness by preventing the development of gastric dysrhythmias and the elevation of plasma vasopressin. Thirteen volunteers with a history of motion sickness underwent circular vection, during which nausea (scored 0-3, i.e., none to severe), electrogastrographic recordings, and plasma vasopressin levels were assessed with or without ginger pretreatment in a crossover-design, double-blind, randomized placebo-controlled study. Circular vection induced a maximal nausea score of 2.5 +/- 0.2 and increased tachygastric activity and plasma vasopressin. Pretreatment with ginger (1,000 and 2,000 mg) reduced the nausea, tachygastria, and plasma vasopressin. Ginger also prolonged the latency before nausea onset and shortened the recovery time after vection cessation. Intravenous vasopressin infusion at 0.1 and 0.2 U/min induced nausea and increased bradygastric activity; ginger pretreatment (2,000 mg) affected neither. Ginger effectively reduces nausea, tachygastric activity, and vasopressin release induced by circular vection. In this manner, ginger may act as a novel agent in the prevention and treatment of motion sickness.

Efficacy of desmopressin (Minirin) in the treatment of nocturia: a double-blind placebo-controlled study in women.
            (Lose et al., 2003) Download
OBJECTIVE:  The purpose of this study was to investigate the efficacy and safety of oral desmopressin in the treatment of nocturia in women. STUDY DESIGN:  Women aged 18 years or older with nocturia (>or=2 voids per night with a nocturia index score >1) received desmopressin (0.1 mg, 0.2 mg, or 0.4 mg) during a 3-week dose-titration period. After a 1-week washout period, patients who responded in this period received desmopressin or placebo in a double-blind fashion for 3 weeks. RESULTS:  In double-blind phase, 144 patients were randomly assigned to groups (desmopressin, n=72; placebo, n=72). For desmopressin, 33 (46%) patients had a 50% or greater reduction in nocturnal voids against baseline levels compared with 5 (7%) patients receiving placebo (P<.0001). The mean number of nocturnal voids, duration of sleep until the first nocturnal void, nocturnal diuresis, and ratios of nocturnal per 24 hours and nocturnal per daytime urine volumes changed significantly in favor of desmopressin versus placebo (P<.0001). In the dose-titration phase headache (22%), nausea (8%), and hyponatremia (6%) were reported. Two deaths occurred, although neither could be directly associated with the study drug. CONCLUSION:  Oral desmopressin is an effective and well-tolerated treatment for nocturia in women.

Vasopressin and memory: improvement in normal short-term recall and reduction of alcohol-induced amnesia.
            (Millar et al., 1987) Download
The vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP) has been shown in healthy male volunteers to cause significant improvement in short-term memory and to reduce alcohol-induced amnesia. There was no significant effect upon semantic retrieval or simple reaction time. It was concluded that vasopressin benefited the initial processes of consolidation and learning, while the reduction of the amnesic effects of alcohol may support the contentions of other authors that the peptide improves memory in states of mild amnesia.


The effect of vasopressin on memory in the healthy elderly.
            (Nebes et al., 1984) Download
The effect that vasopressin has upon memory in young and old males was tested in a double-blind crossover study. There were two 1-week medication periods; during one, subjects received 60 micrograms of vasopressin daily; during the other, placebo. Reaction time tasks were used to measure their speed of retrieval from: short-term memory (STM), long-term memory (LTM), and semantic memory (SM). While vasopressin did not affect SM retrieval time or simple vocal reaction time, it did reduce memory comparison time and perceptual-motor time in STM and retrieval time in LTM. The degree of facilitation was similar in young and old.

Enuresis, sleep and desmopressin treatment.
            (Nevéus et al., 2002) Download
AIM:  To detect effects of desmopressin on sleep in enuretic children and to look for polysomnographical differences between responders and non-responders to desmopressin treatment. METHODS:  Twenty-one children with primary nocturnal enuresis were examined polysomnographically before treatment. All but one of the children then received treatment with desmopressin in standard dosage, and the response was documented. Seven of the children underwent a second polysomnographic registration while on treatment. RESULTS:  The time interval (+/- 1 SD) between sleep onset and the enuretic episode was 92 +/- 67 min without medication and 372 +/- 157 min when desmopressin was given (p = 0.003). Standard polysomnographic variables were not affected by the drug. Ten children were desmopressin responders and 10 were non-responders. The total sleep time was 455 +/- 56 min in the former and 408 +/- 31 min in the latter group (p = 0.04). The responders spent 27.4 +/- 5.5% of their total sleep time in rapid eye movement sleep, compared with 18.2 +/- 6.5% in the non-responder group (p = 0.004). CONCLUSION:  Desmopressin has no major effects on sleep as such but does delay bladder emptying. Enuretic children responding to desmopressin treatment have more rapid eye movement sleep than therapy-resistant children.

Improvement of sleep and pituitary-adrenal inhibition after subchronic intranasal vasopressin treatment in elderly humans.
            (Perras et al., 2003) Download
Subchronic intranasal treatment with argininevasopressin (AVP) has been shown to exert a strong ameliorating effect on sleep and slow wave sleep (SWS) deficits in elderly. However, AVP is also a potent stimulus of the pituitary-adrenal stress system, which is usually inhibited during early, SWS-rich sleep. A disinhibition of pituitary-adrenal activity during sleep is correlated with aging and is considered a pathologic factor contributing to various age-related diseases. Here, we examined whether the beneficial effect of prolonged intranasal AVP administration on sleep in aged would be associated with a concomitant decrease in pituitary-adrenal inhibition and effects on other neuroendocrine features of sleep. Twenty-six healthy elderly (mean 72.9 yr) with mild sleep complaints were investigated in a placebo controlled double-blind study. One group was treated daily each morning and evening with intranasal AVP (2 x 20 IU) for 10 weeks, the other received placebo. During polysomnographical recordings taken at the beginning and end of the treatment period, blood was sampled every 15 min. Intranasal AVP increased SWS on average by +21.5 min (p<0.02). The effect persisted on the night after acute withdrawal of the peptide treatment with no rebound occurring. Notably, rather than increasing pituitary-adrenal activity, AVP decreased the early sleep cortisol nadir on average by 0.5 microg/dl (p<0.05). AVP did not induce any measurable changes in fluid balance or cardiovascular activity. Overall, results indicate a promoting effect of AVP on SWS in aged accompanied by a beneficial rather than impairing influence on the neuroendocrine pattern of sleep.

Brain potential changes after intranasal vs. intravenous administration of vasopressin: evidence for a direct nose-brain pathway for peptide effects in humans.
            (Pietrowsky et al., 1996)  Download
There is evidence that intranasal application of peptides is a way to circumvent the blood-brain barrier. This led us to compare the effects of arginine-vasopressin (AVP) on event-related potentials (ERPs) in healthy men (n = 15) after intranasal and after intravenous (i.v.) administration. In a double-blind, crossover study, subjects received on three different occasions 20 IU of AVP intranasally (IN), 1.5 IU of AVP i.v., and saline solution. ERPs were recorded during the subject's performance on a auditory attention task. Plasma concentrations of vasopressin during task performance were enhanced after AVP, with the increase after i.v. administration of AVP exceeding that after AVP (p < 0.05). Intranasal administration of AVP substantially increased the P3 component of the ERP (p < 0.05). Intranasal administration of AVP substantially increased the P3 component of the ERP (< 0.01). By contrast, i.v. administration of AVP had no consistent effects on the ERP responses. In supplementary experiments as well, i.v. administration of lower doses of AVP (0.1 and 0.025 IU) did not affect the ERP. Plasma vasopressin concentrations after the 0.025 IU dose in these experiments were comparable to those after intranasal administration of 20 IU AVP. The results provide functional evidence that in the human brain effects of peptides like AVP may be facilitated after IN as compared to i.v. administration.


 

Influence of plasma amino acid level on vasopressin secretion.
            (Schmitt et al., 2003)  Download
OBJECTIVES:  Vasopressin (VP) is known to be elevated in patients with diabetes mellitus (DM). While the influence of acute hyperglycemia has been ruled out, the mechanism or the osmotically active compound responsible for the increase in VP secretion is still not elucidated. Because the plasma level of several amino acids (AAs) is increased in DM, we evaluated whether AAs could represent an effective osmotic stimulus for VP secretion. RESEARCH DESIGN AND METHODS:  In a cross-over study, eight healthy volunteers randomly received an infusion of isotonic saline (control) or mixed AA solution, i.v., at a low or a high rate (2 or 4.5 mg/min/kg BW, respectively). Plasma VP (P(VP)) was measured for two hours before and three hours during AA or control infusion. RESULTS:  AA infusion induced a dose-dependent elevation in plasma AA concentration but did not alter P(VP). However, effective plasma osmolality (P(osm)) (osmolality minus urea concentration) remained unchanged because a concommittant fall in plasma sodium concentration (P(Na)), likely due to sodium-linked uptake of AA in peripheral cells, compensated for the rise in plasma AA. CONCLUSION:  The stability of effective P(osm) may explain the lack of change observed in P(VP). Because sodium is a very efficient stimulus for VP secretion, it may be assumed that the fall in P(Na) occurring during AA infusion should have reduced VP secretion and thus P(VP). In this setting, the stability of P(VP) suggests that AAs induced an increase in VP secretion which counterbalanced the fall attributable to the decrease in P(Na). In conclusion, in acute experiments, AAs seem to represent an effective stimulus for VP secretion, almost equally potent as sodium. Further studies are needed to evaluate their contribution to the high P(VP) seen in the chronic setting of DM.

Sentence memory affected by vasopressin analog (DDAVP) in cross-over experiment.
            (Till and Beckwith, 1985) Download
DDAVP has been shown to facilitate memory, especially retrieval, in humans. Healthy young male adult subjects received DDAVP (60 micrograms) in a cross-over design with a one-week interval between sessions. Results indicated that DDAVP improved immediate memory during the first but not the second testing session, particularly for low-verbal subjects. Treatment with DDAVP also facilitated delayed (one-week) recall in the opposite group, a cross-over interaction that suggests a retrieval locus for the DDAVP effect. Furthermore, since DDAVP improved immediate memory more for low-verbal subjects and delayed memory more for high-verbal subjects, it appears that individual difference factors will be important in understanding the effects of vasopressin on memory.


 

Neuropsychological performance and plasma cortisol, arginine vasopressin and oxytocin in patients with major depression.
            (Van Londen et al., 1998) Download
BACKGROUND:  The aim of the study was to search for the existence of, and define, a possible relationship between performance in neuropsychological tests and baseline concentrations of plasma cortisol, vasopressin and oxytocin in medication-free patients with a major depressive episode. METHODS:  Measures of depression and anxiety were obtained and a neuropsychological battery was presented. Blood for neuropeptide analysis was drawn by venepuncture at 8.00, 16.00 and 23.00 h. RESULTS:  The melancholic patients performed less well on the neuropsychological battery than did the non-melancholic patients, but these differences could be accounted for by the severity of the illness. Global intellectual functioning was negatively correlated with mean baseline plasma concentrations of cortisol. Patients with high mean plasma vasopressin concentrations remembered more auditory presented words in the delayed recall test and produced more intrusions in the visual word learning list than did patients with low or normal mean plasma vasopressin concentrations. No association was found between neuropsychological performance and plasma concentrations of oxytocin. CONCLUSIONS:  Our findings support the hypothesis that elevated baseline plasma cortisol concentrations are related to cognitive impairment in depressed patients and the hypothesis that the neuropeptide vasopressin independently enhances memory, directly or indirectly through increasing arousal and attention.

Effect of intranasal arginine vasopressin on human headache.
            (Yang et al., 2012)  Download
Arginine vasopressin (AVP), a nonapeptide hormone of posterior pituitary, reaches the central nervous system from systemic blood circulation with a difficulty because of the blood-brain barrier (BBB). The interest has been expressed in the use of the nasal route for delivery of AVP to the brain directly, exploiting the olfactory pathway. Our previous study has demonstrated that AVP in the brain rather than the spinal cord and blood circulation plays an important role in rat pain modulation. For understanding the role of AVP on pain modulation in human, the communication tried to investigate the effect of intranasal AVP on human headache. The results showed that (1) AVP concentration in both plasma and cerebrospinal fluid (CSF) increased significantly in headache patients, who related with the headache level; (2) there was a positive relationship between plasma and CSF AVP concentration in headache patients; and (3) intranasal AVP could relieve the human headache in a dose-dependent manner. The data suggested that intranasal AVP, which was delivered to the brain through olfactory region, could treat human headache and AVP might be a potential drug of pain relief by intranasal administration.


References

Becker, B and RE Christensen (1956), ‘Beta hypophamine (vasopressin), its effect upon intraocular pressure and aqueous flow in normal and glaucomatous eyes.’, AMA Arch Ophthalmol, 56 (1), 1-9. PubMed: 13338918
Forsling, ML, et al. (1998), ‘Daily patterns of secretion of neurohypophysial hormones in man: effect of age.’, Exp Physiol, 83 (3), 409-18. PubMed: 9639350
Laczi, F, et al. (1982), ‘Effects of lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin on memory in healthy individuals and diabetes insipidus patients.’, Psychoneuroendocrinology, 7 (2-3), 185-93. PubMed: 7178372
Laczi, F, et al. (1983), ‘Effects of desglycinamide-arginine-vasopressin (DG-AVP) on memory processes in diabetes insipidus patients and non-diabetic subjects.’, Acta Endocrinol (Copenh), 102 (2), 205-12. PubMed: 6829260
Lien, HC, et al. (2003), ‘Effects of ginger on motion sickness and gastric slow-wave dysrhythmias induced by circular vection.’, Am J Physiol Gastrointest Liver Physiol, 284 (3), G481-9. PubMed: 12576305
Lose, G, et al. (2003), ‘Efficacy of desmopressin (Minirin) in the treatment of nocturia: a double-blind placebo-controlled study in women.’, Am J Obstet Gynecol, 189 (4), 1106-13. PubMed: 14586363
Millar, K, WJ Jeffcoate, and CP Walder (1987), ‘Vasopressin and memory: improvement in normal short-term recall and reduction of alcohol-induced amnesia.’, Psychol Med, 17 (2), 335-41. PubMed: 3602225
Nebes, RD, CF Reynolds, and LC Horn (1984), ‘The effect of vasopressin on memory in the healthy elderly.’, Psychiatry Res, 11 (1), 49-59. PubMed: 6584931
Nevéus, T, G Bader, and U Sillén (2002), ‘Enuresis, sleep and desmopressin treatment.’, Acta Paediatr, 91 (10), 1121-25. PubMed: 12434900
Perras, B, et al. (2003), ‘Improvement of sleep and pituitary-adrenal inhibition after subchronic intranasal vasopressin treatment in elderly humans.’, J Clin Psychopharmacol, 23 (1), 35-44. PubMed: 12544374
Pietrowsky, R, et al. (1996), ‘Brain potential changes after intranasal vs. intravenous administration of vasopressin: evidence for a direct nose-brain pathway for peptide effects in humans.’, Biol Psychiatry, 39 (5), 332-40. PubMed: 8704064
Schmitt, F, et al. (2003), ‘Influence of plasma amino acid level on vasopressin secretion.’, Diabetes Metab, 29 (4 Pt 1), 352-61. PubMed: 14526263
Till, RE and BE Beckwith (1985), ‘Sentence memory affected by vasopressin analog (DDAVP) in cross-over experiment.’, Peptides, 6 (3), 397-402. PubMed: 4070014
Van Londen, L, et al. (1998), ‘Neuropsychological performance and plasma cortisol, arginine vasopressin and oxytocin in patients with major depression.’, Psychol Med, 28 (2), 275-84. PubMed: 9572085
Yang, J, et al. (2012), ‘Effect of intranasal arginine vasopressin on human headache.’, Peptides, 38 (1), 100-4. PubMed: 22963731