Dimerization of hub protein DYNLL1 and bZIP transcription factor CREB3L1 enhances transcriptional activation of CREB3L1 target genes like arginine vasopressin.

bZIP transcription factors can function as homodimers or heterodimers through interactions with their disordered coiled-coil domain. Such dimer assemblies are known to influence DNA-binding specificity and/or the recruitment of binding partners, which can cause a functional switch of a transcription factor from being an activator to a repressor. We recently identified the genomic targets of a bZIP transcription factor called CREB3L1 in rat hypothalamic supraoptic nucleus by ChIP-seq. The objective of this study was to investigate the CREB3L1 protein-to-protein interactome of which little is known. For this approach, we created and screened a rat supraoptic nucleus yeast two-hybrid prey library with the bZIP region of rat CREB3L1 as the bait. Our yeast two-hybrid approach captured five putative CREB3L1 interacting prey proteins in the supraoptic nucleus. One interactor was selected by bioinformatic analyses for more detailed investigation by co-immunoprecipitation, immunofluorescent cellular localisation, and reporter assays in vitro. Here we identify dimerisation hub protein Dynein Light Chain LC8-Type 1 as a CREB3L1 interacting protein that in vitro enhances CREB3L1 activation of target genes.

Peptides and primate personality: Central and peripheral oxytocin and vasopressin levels and social behavior in two baboon species (Papio hamadryas and Papio anubis).

The neurohormones oxytocin (OT) and arginine vasopressin (AVP) are involved in social behaviors and psychiatric conditions. However, more research on nonhuman primates with complex social behaviors is needed. We studied two closely-related primate species with divergent social and mating systems; hamadryas baboons (Papio hamadryas, n=38 individuals) and anubis baboons (Papio anubis, n=46). We measured OT in cerebrospinal fluid (CSF, n=75), plasma (n=81) and urine (n=77), and AVP in CSF (n=45), and we collected over 250 hours of focal behavioral observations. Using Bayesian multivariate models, we found no clear species difference in hormone levels; the strongest support was for hamadryas having higher CSF OT levels than anubis (posterior probability [PP] for females = 0.75, males = 0.84). Looking at nine specific behaviors, OT was associated with affiliative behaviors (approach, proximity, grooming, PP ∼ 0.85 - 1.00), albeit inconsistently across sources of measurement (CSF, plasma, and urine, which were uncorrelated with each other). Most behaviors had low repeatability (R ∼ 0 - 0.2), i.e. they did not exhibit stable between-individual differences (or "personality"), and different behaviors did not neatly coalesce into higher-order factors (or "behavioral syndromes"), which cautions against the use of aggregate behavioral measures and highlights the need to establish stable behavioral profiles when testing associations with baseline hormone levels. In sum, we found some associations between peptides and social behavior, but also many null results, OT levels from different sources were uncorrelated, and our behavioral measures did not indicate clear individual differences in sociability.

Central diabetes insipidus (vasopressin deficiency) after surgery for pituitary tumours: a systematic review and meta-analysis.

OBJECTIVE: Central diabetes insipidus or vasopressin deficiency (AVP-D) is the most frequent water balance disorder after transsphenoidal surgery (TSS) with variable prevalence amongst studies. We aimed to determine rates of newly developed transient or permanent AVP-D in patients with pituitary tumours treated with TSS. DESIGN AND METHODS: We performed systematic review of Medline, Embase, and Cochrane Library between January 1, 2000 and January 31, 2021 for studies reporting on outcomes for pituitary adenoma, craniopharyngioma, and Rathke's cleft cyst (RCC) after TSS and providing definition of post-operative AVP-D. We pooled the results as proportions with 95% confidence intervals (CIs) using Freeman-Tukey transformation random effects meta-analysis. RESULTS: From 11 694 studies, 51 were included. Rates of transient or permanent AVP-D were: 17% (95% CI, 13-21) and 3% (95% CI, 2-5) in total group, 16% (95% CI, 12-21) and 2% (95% CI, 2-3) in pituitary adenomas, 31% (95% CI, 24-39) and 30% (95% CI, 22-39) in craniopharyngiomas, and 35% (95% CI, 16-57) and 14% (95% CI, 6-23) in RCCs, respectively. Based on diagnostic criteria, rates of transient or permanent AVP-D were: For hypotonic polyuria, 14% (95% CI, 8-22) and 3% (95% CI, 1-4), for hypotonic polyuria and hypernatraemia, 21% (95% CI, 13-29) and 5% (95% CI, 2-11), and for desmopressin administration, 22% (95% CI, 15-29) and 9% (95% CI, 0-30), respectively. CONCLUSIONS: Following TSS, a small proportion of patients with pituitary adenoma have permanent AVP-D (2%), but prevalence reaches 30% in ones with craniopharyngioma and 14% in those with RCC. Diagnostic criteria for post-operative AVP-D remain variable affecting reported rates of this condition.

Arginine vasopressin activates serotonergic neurons in the dorsal raphe nucleus during neonatal development in vitro and in vivo.

Birth stress is a risk factor for psychiatric disorders and associated with exaggerated release of the stress hormone arginine vasopressin (AVP) into circulation and in the brain. In perinatal hippocampus, AVP activates GABAergic interneurons which leads to suppression of spontaneous network events and suggests a protective function of AVP on cortical networks during birth. However, the role of AVP in developing subcortical networks is not known. Here we tested the effect of AVP on the dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT, serotonin) system in male and female neonatal rats, since early 5-HT homeostasis is critical for the development of cortical brain regions and emotional behaviors. We show that AVP is strongly excitatory in neonatal DRN: it increases excitatory synaptic inputs of 5-HT neurons via V1A receptors in vitro and promotes their action potential firing through a combination of its effect on glutamatergic synaptic transmission and a direct effect on the excitability of these neurons. Furthermore, we identified two major firing patterns of neonatal 5-HT neurons in vivo, tonic regular firing and low frequency oscillations of regular spike trains and confirmed that these neurons are also activated by AVP in vivo. Finally, we show that the sparse vasopressinergic innervation in neonatal DRN originates exclusively from cell groups in medial amygdala and bed nucleus of stria terminalis. Hyperactivation of the neonatal 5-HT system by AVP during birth stress may impact its own functional development and affect the maturation of cortical target regions, which may increase the risk for psychiatric conditions later on.

Urinary hyaluronidase activity is closely related to vasopressinergic system following an oral water load in men: a potential role in blood pressure regulation and early stages of hypertension development.

Introduction: Blood pressure (BP) regulation is a complex process involving several factors, among which water-sodium balance holds a prominent place. Arginin-vasopressin (AVP), a key player in water metabolism, has been evoked in hypertension development since the 1980s, but, to date, the matter is still controversial. Hyaluronic acid metabolism has been reported to be involved in renal water management, and AVP appears to increase hyaluronidase activity resulting in decreased high-molecular-weight hyaluronan content in the renal interstitium, facilitating water reabsorption in collecting ducts. Hence, our aim was to evaluate urinary hyaluronidase activity in response to an oral water load in hypertensive patients (HT, n=21) compared to normotensive subjects with (NT+, n=36) and without (NT-, n=29) a family history of hypertension, and to study its association with BP and AVP system activation, expressed by serum copeptin levels and urine Aquaporin 2 (AQP2)/creatinine ratio. Methods: Eighty-six Caucasian men were studied. Water load test consisted in oral administration of 15-20 ml of water/kg body weight over 40-45 min. BP, heart rate, serum copeptin, urine hyaluronidase activity and AQP2 were monitored for 4 hours. Results: In response to water drinking, BP raised in all groups with a peak at 20-40 min. Baseline levels of serum copeptin, urinary hyaluronidase activity and AQP2/creatinine ratio were similar among groups and all decreased after water load, reaching their nadir at 120 min and then gradually recovering to baseline values. Significantly, a blunted reduction in serum copeptin, urinary hyaluronidase activity and AQP2/creatinine ratio was observed in NT+ compared to NT- subjects. A strong positive correlation was also found between urinary hyaluronidase activity and AQP2/creatinine ratio, and, although limited to the NT- group, both parameters were positively associated with systolic BP. Discussion: Our results demonstrate for the first time the existence in men of a close association between urinary hyaluronidase activity and vasopressinergic system and suggest that NT+ subjects have a reduced ability to respond to water loading possibly contributing to the blood volume expansion involved in early-stage hypertension. Considering these data, AVP could play a central role in BP regulation by affecting water metabolism through both hyaluronidase activity and AQP2 channel expression.

Copeptin's role in traumatic brain injury: The promising quest for a new biomarker.

OBJECTIVE: Traumatic brain injury (TBI) necessitates reliable biomarkers to improve patient care. This study explored copeptin as a potential biomarker in TBI and its relation to vasopressin (ADH) in such patients. METHODS: A cross-sectional study was conducted on 50 TBI patients. Exclusion criteria included specific medical conditions and recent traumatic events. Copeptin and ADH testing were performed within 30 days post-trauma. Patient data, Glasgow Coma Scale (GCS) scores, imaging results, and the need for surgical intervention were obtained from medical charts. RESULTS: Copeptin levels negatively correlated with GCS scores (ρ = - 0.313, p = 0.027), indicating a potential association with trauma severity. Copeptin levels (mean: 3.22 pmol/L, median 2.027 pmol/L, SD = 3.15) tended to be lower than those found in the normal population, suggesting possible neuroendocrine dysfunction post-TBI. ADH levels (mean: 67.93 pmol/L, median 56.474 pmol/L SD = 47.67) were higher than the normal range and associated with the need for surgery (p = 0.048). Surprisingly, copeptin and ADH levels negatively correlated (r = - 0.491; p < 0.001), potentially due to differences in degradation processes and physiological variations in TBI patients. CONCLUSION: Copeptin shows potential as a predictive biomarker for assessing TBI severity and predicting patient outcome. However, its complex relationship with ADH in TBI requires further investigation. Careful interpretation is needed due to potential variations in excretion dynamics and metabolism. Larger studies on TBI patient cohorts are essential to validate copeptin as a reliable biomarker and improve patient care in TBI.

When Thirst Ceases to Exist: A Case Report and Literature Review of Adipsic Diabetes Insipidus Following Coil Embolization of a Ruptured Anterior Communicating Artery Aneurysm.

Diabetes insipidus is a condition characterized by inappropriately dilute urine in the setting of serum hyperosmolality. The two predominant subtypes include central (from lack of vasopressin production) and nephrogenic diabetes insipidus (from renal resistance to circulating vasopressin). A common manifestation is the significant pursuant thirst from excessive polyuria. We present a case report and literature review of an infrequent variation of central diabetes insipidus known as adipsic (hypothalamic) diabetes insipidus, characterized by the absence of thirst, secondary to coiling of a ruptured anterior communicating artery aneurysm. Due to the loss of thirst, patients are at a heightened risk for hypernatremia and complications secondary to dehydration. Our patient's course was complicated by recurrent polyuria and hypernatremia, requiring a fixed-dose desmopressin regimen. On follow-up, only partial thirst sensation was restored. We provide a literature review to compare our case report to the scant literature available to broaden the awareness of this infrequent, perilous, manifestation.

Potential indication of chemotherapy for hypodipsia and arginine vasopressin deficiency secondary to hypothalamic-pituitary Langerhans cell histiocytosis: a case report and literature review.

Hypothalamic-pituitary Langerhans cell histiocytosis (HP-LCH) is often associated with arginine vasopressin deficiency (AVD). Patients with AVD caused by HP-LCH rarely develop an impaired osmotic threshold for thirst (OTT). Improvement in OTT among such patients has not been reported in the literature. To our knowledge, here we report the first case of AVD due to HP-LCH in which hypodipsia resolved during chemotherapy. A nine-year-old Japanese girl presented with polydipsia, polyuria, anorexia, and hypernatremia (149.8 mEq/L) and was diagnosed with AVD secondary to HP-LCH. Visual analog scale examination showed a reduced OTT following the water deprivation test. During chemotherapy for Langerhans cell histiocytosis (LCH), serum sodium concentrations became stable between 138.9 and 142.9 mEq/L under the replacement of desmopressin. Repeated visual analog scale examinations showed that she experienced a sense of thirst at a serum sodium concentration of 142.3-144.6 mEq/L, at which she did not experience any thirst prior to the initiation of chemotherapy. These data suggest that chemotherapy directly improved the OTT in our patient. Improved mechanical compression or infiltration of the hypothalamus related to OTT may lead to the recovery of the sense of thirst. This report highlights the potential role of chemotherapy for solitary HP-LCH in patients with hypodipsia and AVD.

Severe Bradycardia Associated with the Use of Terlipressin: A Case Report.

Introduction: Although terlipressin is known to cause bradycardia, this adverse effect is usually described in association with hypertension and is considered a benign compensatory response mediated by arterial baroreceptors. Cardiac monitoring for patients receiving terlipressin is not routinely recommended. Case Presentation: A 77-year-old female patient with no history of coronary artery disease and no other coexisting risk factors for cardiac arrhythmias or conduction disturbances was admitted to intensive care unit with severe cholangitis, complicated by variceal bleeding. She developed severe sinus bradycardia following the use of terlipressin, which was associated with significant hypotension that required the infusion of norepinephrine. The bradycardia occurred again when terlipressin therapy was reattempted. Conclusion: Vasopressin is known to sensitize baroreceptor reflexes by a central mechanism though its actions on V1a receptors in the area postrema, and we speculate that vasopressin analogues such as terlipressin may act in the same manner. That this effect is not widely described in terlipressin safety literature may be due to the overall younger age range of the trial population. This raises the possibility that cardiac monitoring may be warranted for elderly patients receiving terlipressin.

Paternal absence and increased caregiving independently and interactively shape the development of male prairie voles at subadult and adult life stages.

The influence of maternal caregiving is a powerful force on offspring development. The absence of a father during early life in biparental species also has profound implications for offspring development, although it is far less studied than maternal influences. Moreover, we have limited understanding of the interactive forces that maternal and paternal caregiving impart on offspring. We investigated if behaviorally upregulating maternal care compensates for paternal absence on prairie vole (Microtus ochrogaster) pup development. We used an established handling manipulation to increase levels of caregiving in father-absent and biparental families, and later measured male offspring behavioral outcomes at sub-adulthood and adulthood. Male offspring raised without fathers were more prosocial (or possibly less socially anxious) than those raised biparentally. Defensive behavior and responses to contextual novelty were also influenced by the absence of fathers, but only in adulthood. Offensive aggression and movement in the open field test changed as a function of life-stage but not parental exposure. Notably, adult pair bonding was not impacted by our manipulations. Boosting parental care produced males that moved more in the open field test. Parental handling also increased oxytocin immunoreactive cells within the supraoptic nucleus of the hypothalamus (SON), and in the paraventricular nucleus (PVN) of biparentally-reared males. We found no differences in vasopressinergic cell groups. We conclude that male prairie voles are contextually sensitive to the absence of fathers and caregiving intensity. Our study highlights the importance of considering the ways early experiences synergistically shape offspring behavioral and neural phenotypes across the lifespan.

Vasopressin and cardiovascular autonomic adjustment in chronic hypertensive pregnancy.

Chronic hypertensive pregnancy (CHP) is a growing health issue with unknown etiology. Vasopressin (VP), a nonapeptide synthesized in paraventricular (PVN) and supraoptic nucleus (SON), is a well-known neuroendocrine and autonomic modulator of the cardiovascular system, related to hypertension development. We quantified gene expression of VP and its receptors, V1aR and V1bR, within the PVN and SON in CHP and normal pregnancy, and assessed levels of secreted plasma VP. Also, we evaluated autonomic cardiovascular adaptations to CHP using spectral indices of blood pressure (BPV) and heart rate (HRV) short-term variability, and spontaneous baroreflex sensitivity (BRS). Experiments were performed in female spontaneously hypertensive rats (SHRs) and in normotensive Wistar rats (WRs). Animals were equipped with a radiotelemetry probe for continuous hemodynamic recordings before and during pregnancy. BPV, HRV and BRS were assessed using spectral analysis and the sequence method, respectively. Plasma VP was determined by ELISA whilst VP, V1aR, and V1bR gene expression was analyzed by real-time-quantitative PCR (RT-qPCR). The results show that non-pregnant SHRs exhibit greater VP, V1aR, and V1bR gene expression in both PVN and SON respectively, compared to Wistar dams. Pregnancy decreased VP gene expression in the SON of SHRs but increased it in the PVN and SON of WRs. Pregnant SHRs exhibited a marked drop in plasma VP concentration associated with BP normalization. This triggered marked tachycardia, heart rate variability increase, and BRS increase in pregnant SHRs. It follows that regardless of BP normalization in late pregnancy, SHRs exhibit cardiovascular vulnerability and compensate by recruiting vagal mechanisms. Pregnant SHR dams have reduced expression of VP in SON associated with increased V1bR expression, lower plasma VP, normal BP during late pregnancy and marked signs of enhanced sympathetic cardiac stimulation (increased HR and LFHR variability) and recruitment of vagal mechanisms (enhancement of BRS and HFHR variability).

A novel AVPR2 gene mutation in a Chinese pedigree with nephrogenic diabetes insipidus.

Nephrogenic diabetes insipidus (NDI) is a rare genetic disorder primarily associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin 2 (AQP2) gene, resulting in impaired water reabsorption in the renal tubules. This report describes a case of a young male patient with NDI from China with a history of polydipsia and polyuria for over 15 years. Laboratory examinations of the proband indicated low urine-specific gravity and osmolality. Urologic ultrasound revealed severe bilateral hydronephrosis in both kidneys, bilateral dilatation of the ureters, roughness of the bladder wall, and the formation of muscle trabeculae. The diagnosis of diabetes insipidus was confirmed by water deprivation tests. The administration of posterior pituitary hormone did not alter urine-specific gravity, and osmolality remained at a low level (<300 mOsm/kg). Based on these findings, and the genetic tests of the proband and his parents were performed. A missense mutation (c.616 G>C) in exon 3 of the AVPR2 gene of the proband was found, caused by the substitution of amino acid valine to leucine at position 206 [p.Val206Leu], which was a hemizygous mutation and consistent with X-chromosome recessive inheritance. The administration of oral hydrochlorothiazide improves the symptoms of polydipsia and polyuria in the proband. This novel AVPR2 gene mutation may be the main cause of NDI in this family, which induces a functional defect in AVPR2, and leads to reduced tubular reabsorption of water.

Clinical factors associated with hyponatremia correction during treatment with oral Urea.

BACKGROUND AND HYPOTHESIS: Oral urea is being used more commonly to treat hyponatremia, but factors contributing to the correction rate are unknown. We hypothesized that clinically relevant factors can be identified to help guide hyponatremia correction with oral urea. METHODS: Retrospective study in two university hospitals including hospitalized patients with hyponatremia (plasma sodium < 135 mmol/L) treated with oral urea. Linear mixed-effects models were used to identify factors associated with hyponatremia correction. Rates of overcorrection, osmotic demyelination and treatment discontinuation were also assessed. RESULTS: We included 161 urea treatment episodes in 140 patients (median age 69 years, 46% females, 93% syndrome of inappropriate antidiuresis). Oral urea succeeded fluid restriction in 117 treatment episodes (73%), was combined with fluid restriction in 104 treatment episodes (65%) and was given as only treatment in 27 treatment episodes (17%). A median dose of 30 grams/day of urea for 4 days (interquartile range 2-7 days) increased plasma sodium from 127 to 134 mmol/L and normalized hyponatremia in 47% of treatment episodes. Older age (ß 0.09, 95%CI 0.02 to 0.16), lower baseline plasma sodium (ß -0.65, 95%CI -0.78 to -0.62), and higher cumulative urea dose (ß 0.03, 95%CI -0.02 to -0.03) were independently associated with a greater rise in plasma sodium. Concurrent fluid restriction was associated with a greater rise in plasma sodium only during the first 48 h of treatment (ß 1.81, 95%CI 0.40 to 3.08). Overcorrection occurred in 5 cases (3%), no cases of osmotic demyelination were identified, and oral urea was discontinued in 11 cases (11%) due to side-effects. CONCLUSION: During treatment with oral urea, older age, higher cumulative dose, lower baseline plasma sodium and initial fluid restriction are associated with a greater correction rate of hyponatremia. These factors may guide clinicians to achieve a gradual correction of hyponatremia with oral urea.

Morphological Signatures of Neurogenesis and Neuronal Migration in Hypothalamic Vasopressinergic Magnocellular Nuclei of the Adult Rat.

The arginine vasopressin (AVP)-magnocellular neurosecretory system (AVPMNS) in the hypothalamus plays a critical role in homeostatic regulation as well as in allostatic motivational behaviors. However, it remains unclear whether adult neurogenesis exists in the AVPMNS. By using immunoreaction against AVP, neurophysin II, glial fibrillar acidic protein (GFAP), cell division marker (Ki67), migrating neuroblast markers (doublecortin, DCX), microglial marker (Ionized calcium binding adaptor molecule 1, Iba1), and 5'-bromo-2'-deoxyuridine (BrdU), we report morphological evidence that low-rate neurogenesis and migration occur in adult AVPMNS in the rat hypothalamus. Tangential AVP/GFAP migration routes and AVP/DCX neuronal chains as well as ascending AVP axonal scaffolds were observed. Chronic water deprivation significantly increased the BrdU+ nuclei within both the supraaoptic (SON) and paraventricular (PVN) nuclei. These findings raise new questions about AVPMNS's potential hormonal role for brain physiological adaptation across the lifespan, with possible involvement in coping with homeostatic adversities.

A better understanding of basic science may help our management of LUTS/LUTD in older persons with nocturnal polyuria and nocturia: ICI-RS 2024.

AIMS: To discuss the role of autocrine/paracrine signaling of urothelial arginine vasopressin (AVP) on mammalian bladder capacities and micturition thresholds, impact of distension on water/urea reabsorption from the bladder, review of the literature to better characterize the central/peripheral effects of AVP, desmopressin (dAVP) toxicity, and urine biomarkers of nocturia. METHODS: This review summarizes discussions during an International Consultation on Incontinence-Research Society 2024 think tank with respect to the role of urothelial AVP in aged individuals with nocturnal polyuria, impact of solute and water reabsorption by the bladder on uninterrupted sleep, central effects of AVP, pharmacological basis of dAVP toxicity, and biomarkers in nocturia/lower urinary tract dysfunction (LUTD) with neurological diseases. RESULTS: Consensus recognized AVP function and pathways in the central nervous system (CNS), pre-proAVP localized using immunohistochemistry in bladder sections from adult/aged noncancerous human punch biopsies and rodent bladder sections is likely to accelerate the systemic uptake of water and urea from the bladder of anesthetized mice instilled with 3H-water and 14C-urea. Mechanisms for charged and uncharged solutes and water transport across the bladder, mechanism of dAVP toxicity, and utility of urine biomarkers in those with neurological diseases/nocturia were determined from literature reviews. CONCLUSION: Pre-proAVP is present in human/rodent bladders and may be involved in water reabsorption from bladder that prevents the sensation of fullness for uninterrupted sleep in healthy adults. The mechanism of action of AVP in the CNS was discussed, as was electrolyte/water transport across the bladder, the basis for dAVP toxicity, and feasibility of urine biomarkers to identify nocturia/LUTD with neurological diseases.

Plasma concentrations of peptide hormones: Unrealistic levels of vasopressin (AVP), oxytocin (OXT), and brain natriuretic peptide (BNP).

Hormones are specific molecules measured in biological fluids by elaborate analytical systems requiring meticulous attention. Variation between laboratories can be expected. However, recently published measurements of AVP, OXT, and BNP in human plasma under basal/control conditions include numbers which, between publications, vary by 100-10 000-fold. Generally, the methods descriptions are scant, at best, and provide no information about quality control measures. Clearly, two results describing the same basal hormone concentration by numbers three orders of magnitude apart are incongruent providing reason for concern. Basal concentrations of bioactive AVP, OXT, and BNP in human plasma are in the order of 1-10 pmol/L. Therefore, assay systems applied to plasma must be able to measure concentrations of less than 1 pmol/L with appropriate specificity and accuracy. Basal concentrations of AVP, OXT, and BNP above 100 pmol/L should be reconsidered, as such results do not reflect bioactive hormone levels in humans, rats, or mice. Any concentration above 1000 pmol/L is of concern because such levels of bioactive hormone may be seen only under extreme conditions, if at all.

Changes in peripheral oxytocin and vasopressin during a silent month-long Insight meditation retreat.

Background: Given its putative roles in mediating prosocial behavior, attachment bonds, and stress physiology, oxytocin modulation has been hypothesized to be a biological correlate of the salubrious effects of meditation practice. Here we investigated the effects of a month-long silent meditation retreat on changes in oxytocin, and the related hormone and vasopressin, in relation to psychosocial changes in attachment style, anxiety, personality measures, and feelings of social connectedness with fellow meditators. Methods: Plasma oxytocin and vasopressin and self-report questionnaires were measured in retreat participants (n = 28) at the beginning of, and 3 weeks into, a residential meditation retreat. Control participants (n = 34), who were similar in age, gender, and meditation experience, were also assessed across a 3-week interval. Linear mixed effects models were used to assess outcomes. Results: The retreat group showed a small but significant decrease in oxytocin compared to controls who showed no change. In the retreat group, higher openness to experience at Time 1 predicted greater reductions in oxytocin during the retreat, and lower oxytocin at Time 2 was related to stronger feelings of personal connection with fellow meditators. The changes in oxytocin were not related to attachment style or anxiety. Vasopressin decreased over time across both groups, suggesting no specific effect of retreat. Conclusion: These preliminary findings suggest that meditation training in the context of a silent residential retreat may reduce circulating levels of oxytocin. We interpret this finding from multiple theoretical perspectives, discussing key measurement limitations and proposing future study designs that may help to differentiate the effects of different meditation practices and contexts on oxytocin signaling.

Sodium-Glucose Cotransporter 2 Inhibitor Combined with Conventional Diuretics Ameliorate Body Fluid Retention without Excessive Plasma Volume Reduction.

We previously reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (-1.4 ± 31.5% vs. 31.5 ± 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin-angiotensin-aldosterone and sympathetic nervous systems.

Elevated arginine vasopressin levels surrogate acute lung injury in acute decompensated heart failure.

Activated arginine vasopressin (AVP) pathway worsens congestion in heart failure (HF), but its potential to relieve pulmonary congestion is also reported. The pathophysiological role and prognostic utility of AVP elevation in acute decompensated HF (ADHF) are poorly understood. We prospectively enrolled 52 hospitalized patients for ADHF to investigate the association between acute lung injury (ALI) in ADHF and AVP levels on admission. ALI was defined as respiratory failure leading to death, or requiring a respirator or a more than 12-h non-invasive intermittent positive pressure ventilation (NIPPV) support. In addition, we investigated the prognostic value of AVP levels on admission for cardiovascular death or recurrence of ADHF after discharge. ALI was documented in 7 patients (13.5%) during a median hospital stay of 14 days. And the patients with ALI demonstrated significantly higher AVP levels than those without (32.5 ± 21.6 vs. 6.4 ± 8.7 pg/ml, p = 0.018). Besides, the patients with ALI demonstrated significantly higher heart rates (HR) and lower E/e' on admission (HR: 127 ± 24 vs. 97 ± 28 bpm; E/e': 10.6 ± 3.7 vs. 17.4 ± 6.2, all p < 0.05, respectively). Of note, significant hemodilution assessed by hemoglobin and hematocrit values were observed in the patients with ALI 48 h after admission. A receiver operating characteristic curve analysis showed that higher than 7.2 pg/ml surrogate ALI in ADHF (AUC: 0.897, p = 0.001, Sensitivity: 85.7%, and Specificity: 77.8%). In contrast, increased AVP levels on admission could not predict cardiovascular events after discharge. Elevated AVP levels on admission are associated with ALI in ADHF but not cardiovascular events after discharge.