Lower Arginine Vasopressin Levels Research Articles

Neural control of fluid homeostasis is engaged below 10°C in hibernation.

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) hibernate for several months each winter without access to water,1 but the mechanisms that maintain fluid homeostasis during hibernation are poorly understood. In torpor, when body temperature (TB) reaches 4°C, squirrels decrease metabolism, slow heart rate, and reduce plasma levels of the antidiuretic hormones arginine vasopressin (AVP) and oxytocin (OXT).1 Squirrels spontaneously undergo interbout arousal (IBA) every 2weeks, temporarily recovering an active-like metabolism and a TB of 37°C for up to 48 h.1,2 Despite the low levels of AVP and OXT during torpor, profound increases in blood pressure and heart rate during the torpor-IBA transition are not associated with massive fluid loss, suggesting the existence of a mechanism that protects against diuresis at a low TB. Here, we demonstrate that the antidiuretic hormone release pathway is activated by hypothalamic supraoptic nucleus (SON) neurons early in the torpor-arousal transition. SON neuron activity, dense-core vesicle release from the posterior pituitary, and plasma hormone levels all begin to increase before TB reaches 10°C. Invivo fiber photometry of SON neurons from hibernating squirrels, together with RNA sequencing and c-FOS immunohistochemistry, confirms that SON is electrically, transcriptionally, and translationally active to monitor blood osmolality throughout the dynamic torpor-arousal transition. Our work emphasizes the importance of the antidiuretic pathway during the torpor-arousal transition and reveals that the neurophysiological mechanism that coordinates the hormonal response to retain fluid is active at an extremely low TB, which is prohibitive for these processes in non-hibernators.

Natura Non Facit Saltus: The Adaptive Significance of Arginine Vasopressin in Human Affect, Cognition, and Behavior

Hormones coordinate internal bodily systems with cognition, affect, and behavior, and thereby influence aspects of social interactions including cooperation, competition, isolation, and loneliness. The adaptive significance and contextuality of oxytocin (OXT) and testosterone (T) have been well-studied, but a unified theory and evolutionary framework for understanding the adaptive functions of arginine vasopressin (AVP) remain undeveloped. We propose and evaluate the hypothesis that AVP mediates adaptive variation in the presence and strength of social and sociosexual salience, attention and behavior specifically in situations that involve combinations of cooperation with conflict or competition. This hypothesis can help to explain the ancestral, original functions of AVP-like peptides, and their continuity with the current roles of AVP, for humans, in male-male competition, male-male reciprocity, male-to-female pair bonding, female-female interactions, social integration, and social attention and anxiety. In this context, social isolation and loneliness may be mediated by reduced abilities or interests in navigation of social opportunities and situations, due in part to low AVP levels or reactivity, and in part to reductions in levels of OXT-mediated social reward.

Nephrogenic Syndrome of Inappropriate Antidiuresis Mimicking Hyporeninemic Hypoaldosteronism: Case Report of Two Infants

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an X-linked disease caused by activating mutations in the arginine vasopressin (AVP) receptor-2 (AVPR2) gene. Affected patients excrete concentrated urine despite very low levels of AVP, and consequently develop euvolemic hyponatremia. Due to its low frequency, patients may be misdiagnosed and treated incorrectly. We report two related male infants with NSIAD that was initially confused with hyporeninemic hypoaldosteronism (HH). First, a 2-month-old male presented with hyponatremia, low plasma osmolality, relatively high urine osmolality, and low plasma renin-aldosterone levels. These clinical and laboratory findings were compatible with syndrome of inappropriate antidiuretic hormone (ADH) secretion without apparent cause. Consequently, fludrocortisone was initiated with a presumptive diagnosis of HH. While correcting hyponatremia, fludrocortisone treatment led to hypertension and was discontinued promptly. The second patient, aged one year, was admitted with a history of oligohydramnios, had been hospitalized four times due to hyponatremia since birth, and had a diagnosis of epilepsy. Similarly, the second infant had clinical and laboratory findings compatible with syndrome of inappropriate ADH secretion with no apparent cause. Fluid restriction normalized his serum sodium despite the plasma AVP level being undetectable. In both infants, AVPR2 gene analysis revealed a known mutation (c.409C>T; p.R137C) and confirmed the diagnosis of NSIAD. In conclusion, NSIAD should be considered in all patients with unexplained euvolemic hyponatremia despite high urine osmolality. If NSAID is not considered, the plasma reninaldosterone profile can be confused with HH, especially in infants.

Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia.

Arginine vasopressin (AVP) is released upon osmotic stimulation or hypovolaemia in order to maintain water balance. A recent study showed a role of AVP in haematopoiesis by stimulating red blood cell precursors, suggesting a higher risk of anaemia in patients with AVP deficiency. The objective was to explore the effect of low AVP levels in patients with central diabetes insipidus (cDI) and primary polydipsia (PP) on haemoglobin and the prevalence of anaemia. A total of 164 patients with either cDI (70, 43%) or PP (94, 57%) and 30 healthy volunteers from two prospective diagnostic studies performed in Switzerland, Germany and Brazil were studied. A standardized clinical and biochemical (eg copeptin, full blood count) assessment was performed. Haemoglobin and haematocrit levels and prevalence of anaemia (defined as haemoglobin values of <120g/L in women and <130g/L in men) were analysed. Mean copeptin values were 2.63pmol/L (±1.08) and 3.91pmol/L (±4.28) in patients with cDI and PP and 24.76pmol/L (±5.75) in healthy volunteers, P=.02. The prevalence of anaemia was low in all participants with 7.1%, 2.2% and 10% in cDI, PP and in healthy volunteers, P=.15. Mean haemoglobin values were similar in all groups: 139g/L (±15.85), 140g/L (±13.16) and 139g/L (±13.05) in patients with cDI, PP and healthy volunteers, P=.90, as were mean haematocrit values with 41% in all groups (P=.85). Chronic low AVP levels in patients with cDI and PP do not affect haemoglobin levels and prevalence of anaemia.

Does Arginine Vasopressin Reflect HPA-axis Activation in Major Depressive Disorder?

Researchers have endeavored to subclassify depressive illness based on pathophysiological mechanism. One model relates to hypothalamic-pituitary-adrenal (HPA) axis overactivation with a shift from corticotropin-releasing hormone (CRH) driven regulation to arginine vasopressin (AVP) driven regulation. Given the mixed literature, we compared plasma AVP levels in healthy controls to patients with major depressive disorder (MDD). Plasma samples from 33 patients and 12 controls were collected at baseline, 8 weeks, and 12 weeks of treatment and measured by immunochemical assay. Patients who were treatment responders trended toward lower AVP levels than non-responders. Patients were stratified into low and high AVP groups based on median split. Within the low AVP group, patients whose current episode lasted longer than a year had significantly higher baseline AVP levels than patients whose current episode was less than 6 months. Female patients in the low AVP group had significantly higher baseline AVP levels than male patients. Given the association between stress, HPA axis activation, immune dysregulation, and depression, we also measured concentrations of inflammatory biomarkers. We found a significant negative correlation between IL-10 and baseline AVP levels, within the low AVP subgroup. Given inconsistent data, HPA axis overactivation may be present within a subset of depressed patients.

Plasma oxytocin and vasopressin levels in young and older men and women: Functional relationships with attachment and cognition

A growing literature associates the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) with affiliative and cognitive outcomes. The majority of this work in humans, however, considers these neuropeptides separately. Also, despite evidence that OT and AVP interact with gonadal hormones, still warranted is an examination of sex and age variations in endogenous neuropeptide levels, their interrelations, and their functional relationships with attachment and cognition in humans. This study measured endogenous plasma OT and AVP levels in generally healthy young (18–31 years) and older (63–81 years) men and women to (i) determine levels of and interrelations between OT and AVP; (ii) explore functional relationships with self-reported attachment (attachment anxiety and avoidance) and performance-based cognition (processing speed, verbal memory); and (iii) identify variations in these effects by sex and age. We observed sex- and age-differential patterns of results: Women had higher plasma OT levels than men and older adults had higher plasma AVP levels than young adults. The two neuropeptides were highly negatively intercorrelated across all groups. Functionally, higher AVP levels were associated with greater attachment anxiety and higher OT and lower AVP levels were associated with faster sensorimotor processing speed, with sex and age moderating these effects. This integrated approach identifies variations in endogenous peripheral neuropeptide levels in humans, supporting their sex- and age-specific role as “difference makers” in attachment and cognition.

Low arginine vasopressin levels in patients with central diabetes insipidus is not associated with anaemia

Low arginine vasopressin levels in patients with central diabetes insipidus is not associated with anaemia

Peripheral oxytocin and vasopressin modulates regional brain activity differently in men and women with schizophrenia

BackgroundOxytocin (OT) and arginine vasopressin (AVP) exert sexually dimorphic effects on cognition and emotion processing. Abnormalities in these hormones are observed in schizophrenia and may contribute to multiple established sex differences associated with the disorder. Here we examined sex-dependent hormone associations with resting brain activity and their clinical associations in schizophrenia patients. MethodsOT and AVP serum concentrations were assayed in 35 individuals with schizophrenia (23 men) and 60 controls (24 men) from the Chicago BSNIP study site. Regional cerebral function was assessed with resting state fMRI by measuring the amplitude of low-frequency fluctuations (ALFF) which are believed to reflect intrinsic spontaneous neuronal activity. ResultsIn female patients, lower OT levels were associated with lower ALFF in frontal and cerebellar cortices (p's < 0.05) and in female controls AVP levels were inversely associated with ALFF in the frontal cortex (p = 0.01). In male patients, lower OT levels were associated with lower ALFF in the posterior cingulate and lower AVP levels were associated with lower ALFF in frontal cortex (p's < 0.05). In male controls, lower OT levels were associated with lower ALFF in frontal cortex and higher ALFF in the thalamus (p's < 0.05). There were some inverse ALFF-behavior associations in patients. ConclusionsAlterations in peripheral hormone levels are associated with resting brain physiology in a sex-dependent manner in schizophrenia. These effects may contribute to sex differences in psychiatric symptom severity and course of illness in schizophrenia.

Approach to the Treatment of the Infant With Hyponatremia

Hyponatremia is an electrolyte abnormality that occurs in infancy due to a variety of inherited and acquired disorders. Infants with hyponatremia can present with neurologic symptoms such as vomiting, weakness, and seizures. Common causes of hyponatremia in the infant population are excess ingestion or administration of hypotonic fluids and excessive gastrointestinal salt loss. Hyponatremia in infancy also can be a sign of less common disorders, such as mineralocorticoid deficiency or resistance, and disregulation of arginine vasopressin with impaired free-water removal. Treatment of infants with hyponatremia is dependent on the severity of symptoms and the cause of hyponatremia. In nephrogenic syndrome of inappropriate antidiuresis (NSIAD), fluid retention is due to a gain-of-function mutation in the arginine vasopressin receptor 2 (AVPR2) gene leading to low arginine vasopressin levels. We describe the case of an infant with hyponatremia due to NSIAD, whose mother also has a known mutation in the AVPR2 gene. We report the approach to the treatment of hyponatremia and its unique challenges in infancy.

Arginine vasopressin plasma levels change seasonally in African striped mice but do not differ between alternative reproductive tactics

Arginine vasopressin (AVP) is an important hormone for osmoregulation, while as a neuropeptide in the brain it plays an important role in the regulation of social behaviors. Dry habitats are often the home of obligately sociable species such as meerkats and Damaraland mole-rats, leading to the hypothesis that high plasma AVP levels needed for osmoregulation might be associated with the regulation of social behavior. We tested this in a facultative sociable species, the African striped mouse (Rhabdomys pumilio). During the moist breeding season, both solitary- and group-living reproductive tactics occur in this species, which is obligatory sociable in the dry season. We collected 196 plasma samples from striped mice following different reproductive tactics both during the moist and the dry season. Solitary mice did not have lower AVP levels than sociable mice, rejecting the hypothesis that peripheral AVP is involved in the regulation of alternative reproductive tactics. However, we found significantly higher AVP levels during the dry season, with AVP levels correlated with the abundance of food plants, the main source of water for striped mice. Plasma AVP levels were not correlated with testosterone or corticosterone levels. Our study underlines the important role that AVP plays in osmoregulation, particularly for a free ranging mammal living under harsh arid conditions.

The role of neurohypophysis in the long‐term blood pressure regulation in rats

Evidence suggest that arginine vasopressin (AVP) may contribute to the development and/or maintenance of hypertension in humans and experimental animals. This is partially explained by the antidiuretic (increased vascular volume) and vasopressor effects (increased blood vessels resistance) of AVP. Here we propose that rats with long‐term low blood levels of AVP will cause increases in both; urine output and water intake and diminution of the mean blood pressure (MBP). Young male Wistar rats were divided in sham operated (SHAM) and neurointermediate pituitary lobectomized (NIL) (n=15 in each group). Water intake and urine output where measured once a week by placing the animals in a metabolic box. Five weeks after surgeries MBP was measured by an intra carotid catheter connected to a blood pressure transducer and a data acquisition system (BIOPAC Systems Inc.). AVP, Na+ and K+ serum levels were also measured. Results shown that as compared with SHAM group, NIL animals developed significant low AVP levels, no changes in Na+ and K+ levels and an initial increase in urine output and water intake (diabetes insipidus), to return to normality during second week. In NIL animals a significant diminution of MBP occurred: SHAM, 105±9.2 versus 65±6 mmHg of the NIL animals, p&lt;0.001. These results suggest that neurohypophyseal AVP may be an important factor in the long‐term blood pressure regulation.

Water metabolism disturbances at different stages of primary thyroid failure.

The aim of the present study was to study salt and water metabolism in thyroid deficiency. We performed an oral water loading test (OWL) and a hypertonic 5% saline infusion test (HSI) in 16 patients with overt primary hypothyroidism before replacement treatment (PRE group) and after, in eight patients with subclinical hypothyroidism (SUB group) and in 16 normal individuals (CG group). In the PRE group, a lower free water clearance was detected in the OWL (P < 0.022), with lower plasma osmolality (OWL: P < 0.005; HSI: P < 0.001) and arginine vasopressin (AVP) (OWL: P < 0.001; HSI: P < 0.001) than the CG group, across both tests; they normalized with the replacement treatment. The same plasma abnormalities were detected in the SUB group with the HSI. Although the AVP and thirst thresholds did not differ between the groups, the lag between them was lower in the PRE (4.1+/-3.2 mOsm/kg) and SUB group (2.6+/-2.1 mOsm/kg) than in the CG group (13.3+/-9.2 mOsm/kg) (P < 0.05). There were no differences in atrial natriuretic hormone (ANH), plasma renin activity (PRA) and plasma aldosterone among the groups. These results indicate that plasma hypo-osmolality and low levels of AVP are present in primary hypothyroidism, and indeed are already present in the subclinical phase of the disease. An overlap between the thresholds of thirst and AVP seem to play a role in these abnormalities, but ANH, PRA and plasma aldosterone do not appear to contribute.

Circadian variation of plasma arginine vasopressin concentration, or arginine vasopressin in enuresis.

The objective of these studies was to determine a relationship between primary nocturnal enuresis and arginine vasopressin (AVP) secretion. The first study compared 24-h AVP secretion profiles of enuretic (n = 9) and non-enuretic children (n = 8). Blood samples were collected at 1-h intervals for 24 h. In the second study, nocturnal AVP secretion in group A (n = 40)--with low urinary osmotic pressure (UOP) and large nocturnal urine output (NUO)--was compared with that in group D (n = 11) with normal UOP and small NUO. Plasma AVP levels were measured at 30-min intervals, immediately after falling asleep until 06.00 the following morning. The results of the first study showed that the plasma AVP level was significantly lower (p < 0.05-0.001) in the enuretic group between 23.00 and 04.00. The second study showed that group A had significantly lower AVP levels (p < 0.05-0.001) than group D throughout the night. The mean AVP level during night sleep was 0.64 +/- 0.23 pg/ml in group A and 1.43 +/- 0.66 pg/ml in group D. The results of the first study suggest that decreased nocturnal AVP secretion is a cause of bedwetting. However, the results of the second study suggest that nocturnal enuresis cannot be explained by a decrease in nocturnal AVP secretion alone.

Vasopressin modulation of medullary blood flow and pressure-natriuresis-diuresis in the decerebrated rat.

Studies in our laboratory and others have demonstrated that arginine vasopressin (AVP) exerts potent vasoconstrictor actions on the vessels supplying the renal medulla. The physiological importance of these vascular effects of AVP has been difficult to assess because of high endogenous levels of AVP in anesthetized, surgically prepared animals. We have developed a decerebrated, hypophysectomized, renal-denervated rat model that enables us to study the effects of low levels of AVP on the pressure-diuresis, relationship under acute conditions. These rats maintain normal mean arterial pressure (MAP) and plasma AVP (2.5 pg/ml). Cortical and medullary blood flow (CBF and MBF, respectively) were measured by laser-Doppler flowmetry and total renal blood flow (RBF) by transit time flowmetry. Renal interstitial fluid pressure (RIFP) and urinary sodium excretion (UNaV) responses were determined during controlled increases of MAP produced by aortic occlusion below the renal arteries. From a baseline of 97 +/- 2 mmHg, 30% increases in MAP resulted in a 63% increase in MBF, 35% increase in RIFP, and sixfold increase in UNaV, whereas CBF and RBF remained unchanged. Infusion of AVP (0.50 ng.kg-1.min-1, which increased plasma AVP from normal control levels of 3 pg/ml to 11 pg/ml) produced no change in baseline MAP, RBF, or CBF but lowered MBF by 24%, RIFP by 26%, and UNaV by 71%. The slope of the relationship of AP and UNaV, MBF, and RIP was reduced to nearly zero by these small increases of plasma AVP. We conclude that an increase of plasma AVP in the range that occurs with water restriction decreases MBF selectively and greatly attenuates the arterial pressure-MBF and pressure-natriuretic relationship.

Contents of corticotropin-releasing hormone and arginine vasopressin immunoreactivity in the spleen and thymus during a chronic inflammatory stress

We have previously found that proopiomelanocortin (POMC) mRNA and levels of adrenocorticotropin (ACTH) and β-endorphin peptides are increased in the spleen and thymus of rats with adjuvant-induced arthritis (AA), an immunologically mediated inflammatory disease. To determine whether alterations in immune tissue POMC during AA are also accompanied by changes in immune tissue corticotropin-releasing hormone immunoreactivity (ir-CRH) and arginine vasopressin (AVP), we measured ir-CRH and AVP by radioimmunoassays in spleen and thymic extracts 14 days following injection of adjuvant. Ir-CRH was detectable in all extracts of spleen and thymus. Total contents of ir-CRH in the spleen and thymus were not altered following arthritis, although a significant decrease was observed in splenic extracts from arthritic rats (40.0 ± 4.2 fmol/g tissue) compared to controls (69.5 ± 8.4 fmol/g tissue) when contents were expressed as amount per weight of tissue. Low levels of AVP were also detected in immune tissues, with contents significantly increased in spleens from arthritic animals (17.4 ± 1.6 fmol/g tissue) compared to controls (10.6 ± 1.9 fmol/g) but thymic contents of AVP were not altered by arthritis (10.6 ± 1.3 fmol/g) compared to controls (9.2 ± 0.7 fmol/g). Control levels of AVP were significantly higher in spleens and thymuses from female rats (53 ± 5 and 25 ± 4 fmol/g tissue, respectively) compared to males. G-50 chromatography revealed that the principal form of splenic ir-CRH is CRH(1–41), although in non-arthritic animals some ir-CRH eluted in a position indicating a slightly larger form. Therefore the responses of ir-CRH contents in tissues of the immune system differ from those observed for POMC mRNA and POMC peptide products during this chronic inflammatory stress.

Hyponatremia and Seizures

I was pleased to read the report by David et al1 concerning young infants who developed hyponatremia with seizures. I reported three such cases that appeared to be due to inappropriate secretion of antidiuretic hormone (SIADH).2 David et al1 argued that all of their cases were due to SIADH and presented convincing evidence in three (cases 1, 7, and 8). However, case 6 demonstrated low levels of arginine vasopressin (AVP) and urine sodium concentration. These findings suggest an intake of water greater than the renal excretory capacity.