Rhythm Of Arginine Vasopressin Research Articles

Chapter 21 - Nocturnal enuresis in children: The role of arginine–vasopressin

Nocturnal enuresis is the involuntary pass of urine during sleep beyond the age of 5 years. It is a common condition in childhood and has an impact on the child's well-being. Research into the pathophysiology of the condition in the last decades has led to a paradigm shift, and enuresis is no longer considered a psychiatric disorder but rather a maturation defect with a somatic background. An excess urine production during sleep is a common finding in children with enuresis and disturbances in the circadian rhythm of arginine-vasopressin (AVP) is found in the majority of children with nocturnal polyuria. Children with enuresis and nocturnal polyuria lack the physiologic increase in AVP levels during sleep and treatment with the AVP analogue desmopressin can restore this rhythm and lead to dry nights. The reasons for this aberrant circadian AVP rhythm are not established. Furthermore, not all children with enuresis and nocturnal polyuria can be successfully treated with desmopressin suggesting that factors beyond renal water handling can be implicated such as natriuresis, hypercalciuria, and sleep-disordered breathing. The advances in the research of the genetic background of the condition may shed further light on the enuresis pathophysiology.

Puberty alters renal water handling

We investigated the influence of sex and puberty stage on circadian urine production and levels of antidiuretic hormone [arginine vasopressin (AVP)] in healthy children. Thirty-nine volunteers (9 prepuberty boys, 10 prepuberty girls, 10 midpuberty boys, and 10 midpuberty girls) were included. All participants underwent a 24-h circadian inpatient study under standardized conditions regarding Na(+) and fluid intake. Blood samples were drawn every 4 h for measurements of plasma AVP, serum 17-β-estradiol, and testosterone, and urine was fractionally collected for measurements of electrolytes, aquaporin (AQP)2, and PGE2. We found a marked nighttime decrease in diuresis (from 1.69 ± 0.08 to 0.86 ± 0.06 ml·kg(-1)·h(-1), P < 0.001) caused by a significant nighttime increase in solute-free water reabsorption (TcH2O; day-to-night ratio: 0.64 ± 0.07, P < 0.001) concurrent with a significant decrease in osmotic excretion (day-to-night ratio: 1.23 ± 0.06, P < 0.001). Plasma AVP expressed a circadian rhythm (P < 0.01) with a nighttime increase and peak levels at midnight (0.49 ± 0.05 pg/ml). The circadian plasma AVP rhythm was not influenced by sex (P = 0.56) or puberty stage (P = 0.73). There was significantly higher nighttime TcH2O in prepuberty children. This concurred with increased nighttime urinary AQP2 excretion in prepuberty children. Urinary PGE2 exhibited a circadian rhythm independent of sex or puberty stage. Levels of serum 17β-estradiol and testosterone were as expected for sex and puberty stage, and no effect on the AVP-AQP2-TcH2O axis was observed. This study found a circadian rhythm of plasma AVP independent of sex and puberty stage, although nighttime TcH2O was higher and AQP2 excretion was more pronounced in prepuberty children, suggesting higher prepuberty renal AVP sensitivity.

The influence of high and low levels of estrogen on diurnal urine regulation in young women

BackgroundSex hormones have a pronounced effect on arginine vasopressin (AVP), and therefore on the diurnal water homeostasis. Low and high levels of plasma-estradiol as seen in the follicular phase of the menstrual cycle may therefore alter the diurnal regulation of urine production. Furthermore the structural resemblance of oxytocin to vasopressin has led to speculations about the possible antidiuretic properties of oxytocin under normal physiological conditions. To elucidate the influence of high and low p-estradiol on the regulation of the diurnal urine production, 15 normal menstruating women (21–33 y) underwent two circadian in-patient investigations, both situated in follicular phase.MethodsAdmitting the participants solely in the follicular phase resulted in high and low plasma-estradiol whereas plasma-progesterone was similar. Urine and blood samples were taken at predetermined time points to determine plasma AVP, plasma oxytocin, plasma aldosterone, plasma natriuretic peptide (ANP), urinary solute excretions, and urinary excretions of prostaglandin E2 (PGE-2) and aquaporin-2 (AQP-2). Blood pressure was measured every hour.ResultsPlasma AVP, plasma aldosterone and plasma ANP were unaffected by the different levels of estradiol. All had marked circadian variations whereas oxytocin did not display any circadian rhythm. High estradiol resulted in lower p-osmolality and p-sodium reflecting the downward resetting of the osmoreceptors. Oxytocin did not correlate with either diuresis or urine osmolality. The diurnal urine production was similar in the two groups as were urine osmolality, excretion of PGE-2 and AQP-2. AQP-2 does not have a circadian rhythm and is not significantly correlated to either AVP or oxytocin under normal physiological conditions.ConclusionHigh and low level of estradiol has no influence on the circadian rhythm of AVP or the subsequent urine production. High p-estradiol resets the osmoreceptors for AVP release. Furthermore it appears that oxytocin under normal physiological conditions do not contribute to the overall antidiuretic effect.

Daily and circadian expression of neuropeptides in the suprachiasmatic nuclei of nocturnal and diurnal rodents

The suprachiasmatic nuclei (SCN) of the hypothalamus are necessary for coordination of major aspects of circadian rhythmicity in mammals. Although the molecular clock mechanism of the SCN has been a field of intense research during the last decade, the role of the neuropeptides in the SCN, including arginine–vasopressin (AVP), vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP), in the clock itself or in circadian organization is still largely unknown. Previous studies mainly performed in the rat have examined the profiles of AVP, VIP and GRP mRNA and peptide levels and suggested that the AVP rhythm is controlled by the circadian clock, whereas those of VIP and GRP are directly dependent on lighting conditions. Here, both daily (i.e., under light–dark cycle [LD]) and circadian (i.e., in constant darkness [DD]) profiles of neuropeptide mRNA were investigated in the SCN of the nocturnal mouse Mus musculus and the diurnal rodent Arvicanthis ansorgei to gain insight into a possible role in circadian organization. Our data show that AVP mRNA exhibits a clear circadian rhythm in the SCN peaking by the end of the subjective day in both species. Contrary to what has been observed in rats, oscillations of VIP and GRP mRNA in the SCN are found to be clock-controlled in mice and A. ansorgei, but with different phases for peak expression. While both VIP and GRP mRNA peak during the middle of the subjective night (i.e., with a 6-h lag compared to AVP mRNA) in mice, they peak almost in phase with AVP mRNA in A. ansorgei. Contrary to what has been reported in the rat, mean levels of VIP and GRP peptide mRNA levels tended to be increased by light in the mice. The different circadian organization of SCN neuropeptides mRNA profiles in both light/dark and constant darkness conditions between mice and A. ansorgei could be related with diurnality.

Regional pacemakers composed of multiple oscillator neurons in the rat suprachiasmatic nucleus.

Regional specificities of the dorsal and ventral regions of the suprachiasmatic nucleus (SCN) were examined to elucidate the structure of multioscillator circadian organization. The circadian rhythms of arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) release, and of electrical activity of individual neurons were measured in an organotypic, static slice culture of the SCN obtained from neonatal rats. Five days after the start of culture, robust circadian rhythms were detected in AVP release with a peak located consistently at the middle of the original light phase, while the 24 h profiles of VIP release were either arrhythmic or rhythmic. In the latter case, a phase delay of 5-7 h was observed in the circadian peak from the AVP rhythm. Multi-channel, extracellular recording revealed that 51 (76.1%) out of 67 firing neurons, examined in the SCN, showed circadian rhythms in their firing rate. The percentage of rhythmic neurons was significantly larger in the dorsal (86.8%) than in the ventral (62.1%) region of the SCN, where the AVP and VIP containing neurons predominate, respectively. Twenty-seven percent of the firing rhythms were almost antiphasic from the majority of rhythms. There was no regional specificity in the distribution of the antiphasic rhythm. These findings, that the dorsal and ventral regions of the SCN both contain circadian pacemakers with different properties that regulate the AVP and VIP release separately, is probably due to differences in the number and, hence, the coupling strength of oscillating neurons.

Aging Alters the Rhythmic Expression of Vasoactive Intestinal Polypeptide mRNA But Not Arginine Vasopressin mRNA in the Suprachiasmatic Nuclei of Female Rats

Our laboratory has shown that the ability of the suprachiasmatic nuclei (SCN) to regulate a number of rhythmic processes may be compromised by the time females reach middle age. Therefore, we examined the effects of aging on the rhythmic expression of two neuropeptides synthesized in the SCN, vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP), using in situ hybridization. Because both VIP and AVP are outputs of the SCN, we hypothesized that age-related changes in rhythmicity are associated with alterations in the patterns of expression of these peptides. We found that VIP mRNA levels exhibited a 24 hr rhythm in young females, but by the time animals were middle-aged, this rhythm was gone. The attenuation of rhythmicity was associated with a decline in the level of mRNA per cell and in the number of cells in the SCN producing detectable VIP mRNA. AVP mRNA also showed a robust 24 hr rhythm in young females. However, in contrast to VIP, the AVP rhythm was not altered in the aging animals. The amount of mRNA per cell and the number of cells expressing AVP mRNA also was not affected with age. Based on these results we conclude that (1) various components of the SCN are differentially affected by aging; and (2) age-related changes in various rhythms may be attributable to changes in the ability of the SCN to transmit timing information to target sites. This may explain why the deterioration of various rhythmic processes occurs at different rates and at different times during the aging process.

Circadian Rhythm of Arginine Vasopressin in Hepatorenal Syndrome

The etiology of hepatorenal syndrome is still incompletely understood, but the nonosmotic release of arginine vasopressin (AVP) seems to have an important role. Since AVP presents a well-defined daily periodicity in its production and secretion, the aim of the study was to investigate the circadian rhythm in its circulating plasma concentrations in patients with hepatorenal syndrome, compared with healthy controls. Venous blood samples were drawn during a 24 hour period at 2 hourly intervals from a peripheral vein in 10 healthy subjects and in 10 patients with hepatorenal syndrome for the determination of the circulating plasma levels of AVP by radioimmunoassay. Statistical analysis was carried out by the ‘cosinor’ method. The controls presented a significant (p < 0.002) circadian rhythm in the AVP circulating levels, whereas no rhythm (p > 0.05) was found in patients. The circadian rhythms were significantly (p < 0.005) different between the two groups, patients having higher mean daily concentration and lower circadian variation of AVP. These results confirm the existence of a well-defined circadian rhythm of AVP in healthy subjects, whereas the hepatorenal syndrome patients present a complete loss of the circadian rhythm. It could be hypothesized that primitive damage in circadian time-keeping regulates the circadian rhythm of vasopressinergic neurons, or has a secondary effect on the peripheral vasodilatation in the course of advanced liver disease. This great upset in the temporal and functional organization, together with that of the renin-angiotensin-aldosterone system, could play an important role in promoting and/or in the maintenance of the hydroelectrolyte imbalance that characterizes the hepatorenal syndrome.

Protein synthesis inhibitor phase shifts vasopressin rhythms in long-term suprachiasmatic cultures.

The effects of anisomycin, a protein synthesis inhibitor, on the circadian rhythm of arginine-vasopressin (AVP) release in organotypic slice cultures of the rat suprachiasmatic nucleus were examined. Anisomycin applied to the culture as a 6-h pulse shifted the phase of the AVP rhythm, depending on the circadian phase at which the pulse was given. The resultant phase-response curve consisted of a delay portion throughout the late subjective night and an advance portion in the middle of subjective day. The present findings suggest that protein synthesis is an important process which constitutes the circadian oscillation and/or the input pathway to the circadian pacemaker within the suprachiasmatic nucleus.

Circadian rhythms in the release of vasoactive intestinal polypeptide and arginine-vasopressin in organotypic slice culture of rat suprachiasmatic nucleus

Temporal profiles of the amount of vasoactive intestinal polypeptide (VIP) were examined in the medium of organotypic suprachiasmatic nucleus (SCN) slice cultures over a 2-day period. Arginine-vasopressin (AVP) level was also measured in the same medium. The slices of the SCN were obtained from 7–8-day-old rats and cultured individually in tubes on a roller drum for 14 days. The VIP amount in the medium of SCN culture showed a circadian rhythm with a ∼22-h period. Circadian rhythms with identical periods were also observed in AVP amount of the same culture. However, the peak time of the VIP rhythm was slightly ahead of that of the AVP rhythm. Furthermore, the total VIP amount in the medium over a 24-h period was six times as large as that of AVP. These results suggest that there is a circadian rhythm of VIP which is released from the ventrolateral SCN.

A day/night rhythm of vasopressin and oxytocin in rat retina, pineal and harderian gland

Arginine vasopressin (AVP), oxytocin (OT) and neurophysins (Np) have been found in the pineal gland and the retina of the rat. Because the retina, pineal gland and Harderian gland (HG) serve analogous functions, we undertook a study to determine the presence of these peptides in these three organs of rats. They were detected by two specific methods: HPLC and specific radioimmunoassays. For Np, total neurophysins (NpT) were measured. To determine a 24 hr rhythm, the animals were maintained under a light/dark cycle of 12 hr/12 hr for 3 weeks. The pineal glands, retinae and HG were collected. Day/night rhythms of AVP, OT and NpT were demonstrated in the retina and HG; but the pineal gland had only AVP rhythm. A significant decrease in the rhythms at 4 a.m. was demonstrated in the retina and HG. The 24 hr variation of AVP in the retina seemed parallel to that of the HG.

Neurohypophysial hormones in cerebrospinal fluid of adults: absence of arginine vasotocin and of a diurnal rhythm of arginine vasopressin.

We previously reported a prominent diurnal rhythm of oxytocin (OT) in human cerebrospinal fluid (CSF) similar to the brisk CSF OT rhythm in monkeys. An OT CSF rhythm has not been found in lower species. In contrast, a pronounced arginine vasopressin (AVP) rhythm has been found in lower species, but the AVP CSF rhythm is less marked in subhuman primates. In patients (n = 7) in whom lumbar drains had been temporarily placed for treatment of CSF rhinorrhea, we obtained CSF samples every 6 h. In 6 of these 7 patients, we previously reported (1) finding a prominent CSF OT rhythm, with a peak at 1200 h, by analysis of variance of repeated measures. When the samples of CSF of these same 6 patients (plus 1 additional patient) were assayed for AVP, no AVP rhythm was found. We also measured AVP, OT, and arginine vasotocin (AVT) by RIA in single samples of CSF obtained from 23 other patients. In these single samples of CSF, mean AVP was 0.9 +/- 0.11 (+/- SEM) pg/ml, and OT was 3.7 +/- 0.5 microU/ml. CSF AVT immunoreactivity was 0.6 pg/ml or less in the 23 patients. Two pools of CSF were separated by reverse phase high pressure liquid chromatography. The peak OT and AVP, as determined by RIA, coeluted exactly with synthetic and human posterior pituitary OT and AVP, respectively. No immunoreactive AVT was found in the position of synthetic AVT in the eluates. Thus, OT and AVP are present in human adult CSF, but AVT is not. The lack of a prominent rhythm of AVP in human CSF is in marked contrast to the brisk OT rhythm. The rhythm of neurohypophysial peptides in human and subhuman primates is different from the rhythm in lower species, suggesting different functions for OT and AVP in the central nervous system of various species.

Changes in cerebrospinal fluid levels of vasopressin and oxytocin of the rat during various light-dark regimes

Levels of arginine-vasopressin (AVP) and oxytocin (OXT) in cerebrospinal fluid (CSF) of rats were determined at various times of the day and the night under normal and changed light-dark conditions. During a regular daily 14 h and 10 h dark cycle (lights on 06.00 h, off 20.00 h), AVP in CSF reached a peak at 13.00 h, while the lowest levels were found at 19.00 h), AVP in CSF light-dark cycle into a 14 h dark and 10 h light cycle (lights on 20.00 h, off 06.00 h) did not change the normal AVP rhythm. These lighting conditions elevated the OXT levels in the CSF as compared to those found during a normal light-dark regine, but again no differences were observed between the OXT levels determined at the various time-points. A shift of 6 h of the light-dark cycle (lights on 12.00 h, lights off 02.00 h), completely disrupted the AVP rhythm. However, after 3 weeks of adaptation to this new light-dark regime a high level of AVP in CSF was again observed at 13.00 h, and a low level at 19.00 h. The present data suggest that changes in the normal light-dark conditions affect the levels of neurohypophyseal peptides in the CSF. The results are of interest because of reported changes in memory function induced by alterations in the light-dark cycle.