Plasma Vasopressin Research Articles

Effects of diluted seawater in drinking water on physiological responses, feeding, drinking patterns, and water balance in crossbred dairy goats

Background and Aim: In tropical regions, the intrusion of saline from seawater (SW) due to global warming and sea level rise in recent years is an important natural factor influencing goat well-being. This study aimed to determine the effects of diluted SW in drinking water on the physiological responses and eating and drinking patterns of crossbred dairy goats under tropical conditions. Materials and Methods: Twenty dairy goats were divided into four groups (five animals each) based on body weight and milk yield. Animals received either fresh drinking water (SW0.0, control) or diluted SW at concentrations of 0.5% (SW0.5, low salinity), 1% (SW1.0, moderate salinity), and 1.5% (SW1.5, high salinity). The experiment was performed for 49 days (1st–7th week). Throughout this period, daily food and water intake were measured every day. In addition, blood collection was performed on day 25. Total urine and feces were collected from days 25 to 29. Meal and drinking patterns were determined on days 31 and 32. Results: Salinity did not influence dry matter intake throughout the experiment (p > 0.05). However, SW had a significant effect on eating patterns. The effect of SW on water intake (WI) was pronounced from the 2nd to 7th weeks of this experiment (p < 0.05). The water balance decreased and plasma antidiuretic hormone levels increased from SW1.5 to SW2.5 compared to the other treatments. Rectal temperature and respiration rate increased from 15:00 to 17:00 in SW1.5 patients. The concentrations of plasma electrolyte, creatinine, and heat shock protein 70 did not differ between treatments (p > 0.05). The urinary excretion of Na+ from SW1.5 and K+ and Cl- from SW1.0 was higher than that from SW0.0 and SW0.5 (p < 0.01). Conclusion: Lactating crossbred goats adapted to low and moderate SW by increasing urine volume and urinary electrolyte excretion (Uex), whereas animals responded to high SW by either increasing Uex or altering drinking patterns to minimize salt stress. Keywords: antidiuretic hormone, dairy goat, kidney, saline water, water balance.

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).

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

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. 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. 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. 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.

Elevated blood pressure follows physiological body-water conservation

Background: Pre-clinical evidence suggests that blood pressure (BP) increase is part of an adaptive physiological body response designed to prevent under-hydration. This idea challenges established thinking that hypertension is caused by initial salt-driven over-hydration. We tested the hypothesis that this alternative view also holds true in humans. Methods: In a mechanistic study, we investigated the interrelation between daily Na+ and water intake, renal solute and water excretion, renal water conservation, and body Na+ balance with BP in 6 healthy men living in a controlled environment for 205 days. In an additional daily-life observational study we investigated the interrelation between BP and adaptive-physiological water and Na+ conservation in 108 Singaporeans. Results: In participants living under controlled conditions, BP increased when urine osmolality was high, and fluid intake or urine volume was low. This BP-increasing water conservation response was not caused by body Na+ retention. Similarly, participants living under daily-life conditions showed a BP-elevating adaptive body water conservation response with increased plasma solute concentration, increased plasma vasopressin levels, and reduced urine volume production due to reduced renal free-water excretion. Participants with higher BP relied on more urea and glucose solutes, but on less Na+ solutes, to maintain their hydration status. Participants with essential hypertension showed more pronounced adaptive-physiological water conservation. None of these hypertension-specific water conservation responses were accompanied by differences in 24-h Na+ excretion. Conclusions: BP increase in humans is part of a systemic body water conservation response that occurs largely independent of body Na+ balance. The Mars500 Salt and Water Homeostasis Project was realized by grant support from the German Federal Ministry for Economics and Technology/DLR Forschung unter Weltraumbedingungen (50WB1624-50WB2024) and the Interdisciplinary Centre for Clinical Research (IZKF Junior Research Group 2), Friedrich-Alexander-University of Erlangen-Nuremberg to JT. The food products were donated by APETITO, Coppenrath und Wiese, ENERVIT, HIPP, Katadyn, Kellogg, Molda, and Unilever. The Sodium Storage in Singaporeans Project was realized with grant support from Duke NUS Medical School (Duke-NUS-KBrFA/2019/0026) to JT. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Isotonic hydroxyethyl starch is ineffective in restoring blood pressure during experimental septic shock: Implications for fluid resuscitation strategies

Objectives: The objectives of the study were to evaluate the effect of isotonic or hypertonic hydroxyethyl starch (HES) solutions on blood pressure and to assess the influence of the neurohypophyseal system on this response during experimental septic shock. Male Wistar rats were randomly allocated to undergo either cecal and ligation puncture (CLP) or a simulated surgical procedure (sham). Materials and Methods: Of 6 h post-surgery, either isotonic saline (0.9% sodium chloride, 4 mL/kg), isotonic (HES; at doses of 4, 8 or 16 mL/kg), or hypertonic saline-HES (HS-HES; 4 mL/kg) was administered through the endovenous route, followed by the recording of blood pressure and heart rate. In addition, the levels of sodium, vasopressin, and oxytocin were evaluated after the fluid infusion. Results: The administration of HES did not have a significant effect on blood pressure in our study. However, the HS-HES solution increased plasma osmolality, sodium, vasopressin, and oxytocin levels. Furthermore, the HS-HES induced a transient elevation in blood pressure immediately after infusion, which could be completely blunted by the pre-administration of a V1-vasopressin antagonist. Conclusion: Our results demonstrate that the infusion of an isotonic blood volume expander during experimental septic shock is ineffective in restoring blood pressure due to blood vessel compliance. In contrast, the infusion of a hypertonic solution stimulates vasopressin secretion and can transiently restore blood pressure.

A case of central diabetes insipidus after COVID-19 as a probable diagnosis of lymphocytic infundibulo-neurohypophysitis with positive anti-rabphilin-3A antibodies with review of literature.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, and various complications have been reported. Furthermore, there have been increasing reports of endocrinopathy related to COVID-19 following the pandemic. We report a 49-year-old healthy woman who developed rapid onset of polydipsia and polyuria three weeks after COVID-19. Laboratory tests indicated low urine osmolarity and increased serum osmolarity, and antidiuretic hormone (ADH) was undetectable. Urine osmolality remained low with water deprivation. Similarly, plasma ADH responses to hypertonic-saline infusion were blunted and urine osmolality increased in response to desmopressin. There was no clear evidence of anterior pituitary dysfunction. T1-weighted magnetic resonance imaging (MRI) showed pituitary stalk thickening and absence of posterior pituitary bright signal spots, suggesting the presence of hypophysitis. Based on these results, we made a probable diagnosis of lymphocytic infundibulo-neurohypophysitis (LINH) which have caused central diabetes insipidus. Positive findings for serum anti-rabphilin-3A antibodies, reported as a potential diagnostic marker for LINH, were also noted. Following oral desmopressin administration, polydipsia and polyuria were quickly improved, though treatment with desmopressin was still required over four months. This is the first report of a patient with a probable diagnosis of LINH after COVID-19 who tested positive for anti-rabphilin-3A antibodies. Positive findings for those antibodies suggest that pituitary dysfunction associated with COVID-19 is hypophysitis involving an abnormal immune mechanism. The presence of anti-rabphilin-3A antibodies may be useful as a non-invasive diagnostic marker of LINH and potentially serve as a valuable diagnostic aid in cases of LINH associated with COVID-19.

ENDOCANNABINOID SYSTEM IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS MODULATES AUTONOMIC AND CARDIOVASCULAR CHANGES BUT NOT VASOPRESSIN RESPONSE IN A RAT HEMORRHAGIC SHOCK MODEL.

We evaluated the participation of the endocannabinoid system in the paraventricular nucleus of the hypothalamus (PVN) on the cardiovascular, autonomic, and plasma vasopressin (AVP) responses evoked by hemorrhagic shock in rats. For this, the PVN was bilaterally treated with either vehicle, the selective cannabinoid receptor type 1 antagonist AM251, the selective fatty acid amide hydrolase amide enzyme inhibitor URB597, the selective monoacylglycerol-lipase enzyme inhibitor JZL184, or the selective transient receptor potential vanilloid type 1 antagonist capsazepine. We evaluated changes on arterial pressure, heart rate, tail skin temperature (ST), and plasma AVP responses induced by bleeding, which started 10 min after PVN treatment. We observed that bilateral microinjection of AM251 into the PVN reduced the hypotension during the hemorrhage and prevented the return of blood pressure to baseline values in the posthemorrhagic period. Inhibition of local 2-arachidonoylglycerol metabolism by PVN treatment with JZL184 induced similar effects in relation to those observed in AM251-treated animals. Inhibition of local anandamide metabolism via PVN treatment with URB597 decreased the depressor effect and ST drop induced by the hemorrhagic stimulus. Bilateral microinjection of capsazepine mitigated the fall in blood pressure and ST. None of the PVN treatments altered the increased plasma concentration of AVP and tachycardia induced by hemorrhage. Taken together, present results suggest that endocannabinoid neurotransmission within the PVN plays a prominent role in cardiovascular and autonomic, but not neuroendocrine, responses evoked by hemorrhage.

Characterization of social hierarchy formation and maintenance in same-sex, group-housed male and female C57BL/6 J mice

Social hierarchies are a prevalent feature of all animal groups, and an individual's rank within the group can significantly affect their overall health, typically at the greatest expense of the lowest-ranked individuals, or omegas. These subjects have been shown to exhibit various stress-related phenotypes, such as increased hypothalamic-pituitary axis activity and increased amygdalar corticotropin-releasing factor levels compared to higher-ranked subjects. However, these findings have been primarily characterized in males and in models requiring exhibition of severe aggression. The goals of the current study, therefore, were to characterize the formation and maintenance of social hierarchies using the tube test and palatable liquid competition in same-sex groups of male and female C57BL/6 J mice. We also aimed to examine the effects of tube test-determined social rank on plasma and hypothalamic oxytocin and vasopressin levels, peptides with established roles in social behaviors and the stress response. Lastly, we assessed the effects of environmental enrichment and length of testing on the measures outlined above. Overall, we demonstrated that males and females develop social hierarchies and that these hierarchies can be determined using the tube test. While we were unable to establish a consistent connection between peptide levels and social rank, we observed transient changes in these peptides reflecting complex interactions between social rank, sex, environment, and length of testing. We also found that many male and female omegas began to exhibit passive coping behavior after repeated tube test losses, demonstrating the potential of this assay to serve as a model of chronic, mild psychosocial stress.

Cancer and the Vasopressin Gene: Radioimmunoassay Values and Commentary on Copeptin as a Plasma Marker.

Vasopressin gene expression has been demonstrated to be a common feature of all small-cell lung cancer (SCLC) and breast cancer. Provasopressin (ProVP) is a component of the cancer cell membrane and a likely target for treatment. However, a measurable fraction of this cancer provasopressin is also normally processed and products are released into the circulation. Vasopressin (VP) and vasopressin-associated human neurophysin (VP-HNP), two of three products of processing, were earlier shown to be reliable plasma markers for determining the presence of SCLC and monitoring response to treatment. In this study, copeptin, the third product of provasopressin processing, was preliminarily evaluated as a plasma marker for SCLC or breast cancer using radioimmunoassay (RIA). Antibodies directed against the 18 residue C-terminal peptide fragment of copeptin were used to avoid interference from the large-carbohydrate component of this endogenous glycopeptide. The levels of copeptin in 8 male and 6 female patients with SCLC before treatment ranged from 16 to 319 pmol/L, and these levels were elevated (>2.5 times) in 10 of 14 cases (70%) when compared with healthy volunteers (normal mean, 18 ± 6 pmol/L). Volunteer values for males were smaller than for females (15± 4 pmol/L and 20± 9 pmol/L), but numbers were small. Patients with breast cancer had plasma levels ranging from 12 to 68 pmol/L, with only three of the six elevated. While cancer patients displayed a wide range of plasma copeptin levels over 70% with SCLC and 50% with breast cancer had clearly elevated levels. This finding indicates that for such patients, plasma copeptin, like plasma VP and VP-HNP, could be used to detect disease. The control values found for healthy volunteers using our RIA were in a range predictable from established normal plasma levels of both VP and VP-HNP.

Metabolic effects of vasopressin in pathophysiology of diabetic kidney disease.

The diabetic kidney disease (DKD) is the major cause of the chronic kidney disease (CKD). Enhanced plasma vasopressin (VP) levels have been associated with the pathophysiology of DKD and CKD. Stimulation of VP release in DKD is caused by glucose-dependent reset of the osmostat leading to secondary pathophysiologic effects mediated by distinct VP receptor types. VP is a stress hormone exhibiting the antidiuretic action in the kidney along with broad adaptive effects in other organs. Excessive activation of the vasopressin type 2 (V2) receptor in the kidney leads to glomerular hyperfiltration and nephron loss, whereas stimulation of vasopressin V1a or V1b receptors in the liver, pancreas, and adrenal glands promotes catabolic metabolism for energy mobilization, enhancing glucose production and aggravating DKD. Increasing availability of selective VP receptor antagonists opens new therapeutic windows separating the renal and extra-renal VP effects for the concrete applications. Improved understanding of these paradigms is mandatory for further drug design and translational implementation. The present concise review focuses on metabolic effects of VP affecting DKD pathophysiology.

Aldosterone Contributes to Vasopressin Escape through Changes in Water and Urea Transport.

Hyponatremia (hypo-osmolality) is a disorder of water homeostasis due to abnormal renal diluting capacity. The body limits the degree to which serum sodium concentration falls through a mechanism called "vasopressin escape". Vasopressin escape is a process that prevents the continuous decrease in serum sodium concentration even under conditions of sustained high plasma vasopressin levels. Previous reports suggest that aldosterone may be involved in the vasopressin escape mechanism. The abilities of aldosterone synthase (Cyp11b2) knockout and wild-type mice to escape from vasopressin were compared. Wild-type mice escaped while the aldosterone synthase knockout mice did not. Both the water channel aquaporin 2 (AQP2) and the urea transporter UT-A1 protein abundances were higher in aldosterone synthase knockout than in wild-type mice at the end of the escape period. Vasopressin escape was also blunted in rats given spironolactone, a mineralocorticoid receptor blocker. Next, the role of the phosphatase, calcineurin (protein phosphatase 2B, PP2B), in vasopressin escape was studied since aldosterone activates calcineurin in rat cortical collecting ducts. Tacrolimus, a calcineurin inhibitor, blunted vasopressin escape in rats compared with the control rats, increased UT-A1, AQP2, and pS256-AQP2, and decreased pS261-AQP2 protein abundances. Our results indicate that aldosterone regulates vasopressin escape through calcineurin-mediated protein changes in UT-A1 and AQP2.

The relationship between endogenous oxytocin and vasopressin levels and the Prader-Willi syndrome behaviour phenotype.

Oxytocin and vasopressin systems are altered in Prader Willi syndrome (PWS). However, investigations into endogenous oxytocin and vasopressin levels as well as clinical trials evaluating the effect of exogenous oxytocin on PWS symptoms have had mixed results. It is also unknown whether endogenous oxytocin and vasopressin levels are associated with certain PWS behaviours. We compared plasma oxytocin and vasopressin and saliva oxytocin levels in 30 adolescents and adults with PWS to 30 typically developing age-matched controls. We also compared neuropeptide levels between gender and genetic subtypes within the PWS cohort and examined the relationship between neuropeptide levels and PWS behaviours. While we did not measure a group difference in plasma or saliva oxytocin levels, plasma vasopressin was significantly lower in individuals with PWS compared to controls. Within the PWS cohort, saliva oxytocin levels were higher in females compared to males and individuals with the mUPD compared to the deletion genetic subtype. We also found the neuropeptides correlated with different PWS behaviours for males and females and for genetic subtypes. For the deletion group, higher plasma and saliva oxytocin levels were related to fewer behaviour problems. For the mUPD group, higher plasma vasopressin levels were related to more behaviour problems. These findings support existing evidence of a vasopressin system defect in PWS and for the first time identify potential differences in the oxytocin and vasopressin systems across PWS genetic subtypes.

Input from afferent renal nerves is involved in progression of hypertensive heart failure through central vasopressin-mediated sympathoexcitation

Introduction: Paraventricular nucleus of hypothalamus (PVN), a control center of sympathetic outflow, receives the input from afferent renal nerves. Although acute stimulation of afferent renal nerves increases central sympathetic outflow, it remains unclear if the renal afferents contribute to progression of heart failure. Acute stimulation of afferent renal nerves was reported to increase plasma vasopressin concentration. In addition, central dendritic release of vasopressin by activation of vasopressin-expressing neurons located in the PVN may cause sympathoexcitation via stimulation of neighboring presympathetic neurons in the PVN. Therefore, we hypothesized that the chronic input from afferent renal nerves contributes to sympathoexcitation and hypertensive cardiac dysfunction along with activation of vasopressin-expressing neurons and presympathetic neurons in the PVN. Methods: Male Dahl salt-sensitive rats were fed low salt diet (LS) or 8% high salt diet from 6 weeks of age, and the high salt-fed rats were allocated to selective afferent renal denervation (HS-ARDN) or sham surgery (HS-Sham) at 9 weeks. The effect of ARDN on central sympathetic regulation was investigated at 12 weeks (pre-heart failure phase). In another cohort, its effect on cardiac phenotypes was evaluated at 16 weeks (heart failure phase). Results: At 12 weeks, plasma norepinephrine level was increased in HS-Sham compared to LS and was attenuated by ARDN (LS 188.7±16.5 pg/ml, HS-Sham 563.8±82.7 pg/ml, HS-ARDN 327.4±50.2 pg/ml; n=15, 12, 14; p<0.05). The c-Fos expression, a marker of neuronal activity, in presympathetic neurons in the PVN was also increased in HS-Sham and attenuated in HS-ARDN, which was in parallel with the c-Fos expression in vasopressin-expressing neurons in the PVN. At 16 weeks, the decrease of left ventricular (LV) fractional shortening (HS-Sham 25.9±1.7 % vs LS 46.7±0.6 %, n=9, 9; p<0.01) was improved in HS-ARDN (42.2±1.2 %, n=7; p<0.01 vs HS-Sham). LV weight and lung weight were significantly increased in HS-Sham compared to LS (LV weight/body weight: 4.39±0.19 mg/g vs 2.53±0.03 mg/g; lung weight/body weight: 5.29±0.37 mg/g vs 3.55±0.05 mg/g; p<0.05), and these changes were attenuated in HS-ARDN (LV weight/body weight: 3.73±0.14 mg/g; lung weight/body weight: 4.17±0.11 mg/g; p<0.05 vs HS-Sham). Histological LV fibrosis and fibrosis marker expression, such as connective tissue growth factor, in LV were significantly attenuated in HS-ARDN compared to HS-Sham. ARDN did not significantly impact the high salt-induced blood pressure elevation in both cohorts. Conclusion: The input from afferent renal nerves contributes to cardiac dysfunction, probably via the central vasopressin-mediated sympathoexcitation even without blood pressure changes in hypertensive heart failure model. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Novel signalling pathways in nephrogenic syndrome of inappropriate antidiuresis: functional implication of site-specific AQP2 phosphorylation.

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X-linked disease caused by gain-of-function mutations of arginine vasopressin receptor 2 (V2R). Patients with NSIAD are characterized by the inability to excrete a free water load and by inappropriately increased urinary osmolality despite very low levels of plasma vasopressin, resulting in euvolaemic hyponatraemia. To dissect the signalling downstream V2R constitutively active variants, Flp-In T-REx Madin-Darby canine kidney (FTM) cells, stably transfected with V2R mutants (R137L, R137C and F229V) and AQP2-wt or non-phosphorylatable AQP2-S269A/AQP2-S256A, were used as cellular models. All three activating V2R mutations presented constitutive plasma membrane expression of AQP2-wt and significantly higher basal water permeability. In addition, V2R-R137L/C showed significantly higher activity of Rho-associated kinase (ROCK), a serine/threonine kinase previously suggested to be involved in S269-AQP2 phosphorylation downstream of these V2R mutants. Interestingly, FTM cells expressing V2R-R137L/C mutants and AQP2-S269A showed a significant reduction in AQP2membrane abundance and a significant reduction in ROCK activity, indicating the crucial importance of S269-AQP2 phosphorylation in the gain-of-function phenotype. Conversely, V2R-R137L/C mutants retained the gain-of-function phenotype when AQP2-S256A was co-expressed. In contrast, cells expressing the F229V mutant and the non-phosphorylatable AQP2-S256A had a significant reduction in AQP2membrane abundance along with a significant reduction in basal osmotic water permeability, indicating a crucial role of Ser256 for this mutant. These data indicate that the constitutive AQP2 trafficking associated with the gain-of-function V2R-R137L/C mutants causing NSIAD is protein kinaseA independent and requires an intact Ser269 in AQP2 under the control of ROCK phosphorylation. KEY POINTS: Nephrogenic syndrome of inappropriate antidiuresis is caused by two constitutively active variant phenotypes of AVPR2, one sensitive to vaptans (V2R-F229V) and the other vaptan resistant (V2R-R137C/L). In renal cells, all three activating arginine vasopressin receptor 2 (V2R) variants display constitutive AQP2 plasma membrane expression and high basal water permeability. In cells expressing V2R-R137L/C mutants, disruption of the AQP2-S269 phosphorylation site caused the loss of the gain-of-function phenotype, which, in contrast, was retained in V2R-F229V-expressing cells. Cells expressing the V2R-F229V mutant were instead sensitive to disruption of the AQP2-S256 phosphorylation site. The serine/threonine kinase Rho-associated kinase (ROCK) was found to be involved in AQP2-S269 phosphorylation downstream of the V2R-R137L/C mutants. These findings might have clinical relevance for patients with nephrogenic syndrome of inappropriate antidiuresis.

Relationship between postpartum depression and plasma vasopressin level at 6–8 weeks postpartum: a cross-sectional study

Postpartum depression (PPD) is the most important postpartum mood disorder due to its significant effect on both the infant and family health. Arginine vasopressin (AVP) has been suggested as a hormonal agent involved in the development of depression. The purpose of this study was to investigate the relationship between the plasma concentrations of AVP and the score of Edinburgh Postnatal Depression Scale (EPDS). This cross-sectional study was conducted in 2016–2017 in Darehshahr Township, Ilam Province, Iran. In the first phase, 303 pregnant women, who were at 38 weeks, met the inclusion criteria, and were not depressed (according to their EPDS scores) were included in the study. In the 6–8 week postpartum follow-up, using the EPDS, 31 depressed individuals were diagnosed and referred to a psychiatrist for confirmation. The maternal venous blood samples of 24 depressed individuals still meeting the inclusion criteria and 66 randomly selected non-depressed subjects were obtained to measure their AVP plasma concentrations with ELISA assay. There was a significant positive relationship between plasma AVP levels and the EPDS score (P = 0.000, r = 0.658). Also the mean plasma concentration of AVP was significantly higher in the depressed group (41.35 ± 13.75 ng/ml) than in the non-depressed group (26.01 ± 7.83 ng/ml) (P < 0.001). In a multiple logistic regression model for various parameters, increased vasopressin levels were associated with increased odds of PPD (OR = 1.15, 95% CI = 1.07–1.24, P = 0.000). Furthermore, multiparity (OR = 5.45, 95% CI = 1.21–24.43, P = 0.027) and non-exclusive breastfeeding (OR = 13.06, 95% CI = 1.36–125, P = 0.026) were associated with increased odds of PPD. Maternal gender preference (having a baby of desired and desired sex) decreased the odds of PPD (OR = 0.13, 95% CI = 0.02–0.79, P = 0.027 and OR = 0.08, 95% CI = 0.01–0.5, P = 0.007). AVP seems to be a contributor to clinical PPD by affecting the hypothalamic–pituitary–adrenal (HPA) axis activity. Furthermore, primiparous women had significantly lower EPDS scores.

Renal and Endocrine Responses to Arm Exercise in Persons with Cervical Spinal Cord Injury

The aim of this study was to assess renal functions and endocrine responses to arm exercise in persons with cervical spinal cord injury (CSCI) under euhydrated conditions (free drinking of water), and to determine the physiological effects of exercise on renal function in these subjects. Eleven CSCI individuals (spinal lesions between C6 and C8, American Spinal Injury Association impairment scale A) and nine able-bodied (AB) persons rested for 30 min before performing 30 min arm-crank ergometer exercises at 50% of their maximum oxygen consumption, followed by 60-min of rest/recovery. Urine and blood samples were collected before and immediately after the exercise and recovery period. The CSCI patients showed no increase in plasma adrenaline and plasma renin activity compared with the AB controls, but showed similar changes in plasma aldosterone and the plasma antidiuretic hormone in response to the exercise. Creatinine clearance, osmolal clearance, free water clearance, and the fractional excretion of Na+ did not change during exercise in both groups of subjects, however free water clearance in the CSCI group was higher than in the AB group throughout the study. These findings suggested that activated plasma aldosterone without an increase in adrenaline or renin activity during exercise in CSCI individuals may reflect an adaptation to the disturbance of the sympathetic nervous system to compensate for renal function. As a result, no adverse effects of exercise on renal function in CSCI patients were observed.

Masked Randomized Trial of Epinephrine versus Vasopressin in an Ovine Model of Perinatal Cardiac Arrest.

Current neonatal resuscitation guidelines recommend the use of epinephrine for bradycardia/arrest not responding to ventilation and chest compressions. Vasopressin is a systemic vasoconstrictor and is more effective than epinephrine in postnatal piglets with cardiac arrest. There are no studies comparing vasopressin with epinephrine in newly born animal models with cardiac arrest induced by umbilical cord occlusion. Objective: To compare the effect of epinephrine and vasopressin on the incidence and time to return of spontaneous circulation (ROSC), hemodynamics, plasma drug levels, and vasoreactivity in perinatal cardiac arrest. Design/Methods: Twenty-seven term fetal lambs in cardiac arrest induced by cord occlusion were instrumented and resuscitated following randomization to epinephrine or vasopressin through a low umbilical venous catheter. Results: Eight lambs achieved ROSC prior to medication. Epinephrine achieved ROSC in 7/10 lambs by 8 ± 2 min. Vasopressin achieved ROSC in 3/9 lambs by 13 ± 6 min. Plasma vasopressin levels in nonresponders were much lower than responders after the first dose. Vasopressin caused in vivo increased pulmonary blood flow and in vitro coronary vasoconstriction. Conclusions: Vasopressin resulted in lower incidence and longer time to ROSC compared to epinephrine in a perinatal model of cardiac arrest supporting the current recommendations for exclusive use of epinephrine in neonatal resuscitation.

Vasoplegic Syndrome after Cardiopulmonary Bypass in Cardiovascular Surgery: Pathophysiology and Management in Critical Care.

Vasoplegic syndrome (VS) is a common complication following cardiovascular surgery with cardiopulmonary bypass (CPB), and its incidence varies from 5 to 44%. It is defined as a distributive form of shock due to a significant drop in vascular resistance after CPB. Risk factors of VS include heart failure with low ejection fraction, renal failure, pre-operative use of angiotensin-converting enzyme inhibitors, prolonged aortic cross-clamp and left ventricular assist device surgery. The pathophysiology of VS after CPB is multi-factorial. Surgical trauma, exposure to the elements of the CPB circuit and ischemia-reperfusion promote a systemic inflammatory response with the release of cytokines (IL-1β, IL-6, IL-8, and TNF-α) with vasodilating properties, both direct and indirect through the expression of inducible nitric oxide (NO) synthase. The resulting increase in NO production fosters a decrease in vascular resistance and a reduced responsiveness to vasopressor agents. Further mechanisms of vasodilation include the lowering of plasma vasopressin, the desensitization of adrenergic receptors, and the activation of ATP-dependent potassium (KATP) channels. Patients developing VS experience more complications and have increased mortality. Management includes primarily fluid resuscitation and conventional vasopressors (catecholamines and vasopressin), while alternative vasopressors (angiotensin 2, methylene blue, hydroxocobalamin) and anti-inflammatory strategies (corticosteroids) may be used as a rescue therapy in deteriorating patients, albeit with insufficient evidence to provide any strong recommendation. In this review, we present an update of the pathophysiological mechanisms of vasoplegic syndrome complicating CPB and discuss available therapeutic options.

Reducing Venous Return Using BFR: Alterations In Blood Volume Regulating Hormones And Short-term Training Responses

Partitioning blood from central circulation to the legs via blood flow restricted (BFR) exercise will impact venous return acutely, though the relationship between occlusion pressure and reduced venous return is unknown. A reduction in central volume, which can be tracked by measuring ventricular filling, is likely to affect renin and anti-diuretic hormone (ADH) concentrations, that regulate blood volume via water retention. Blood volume has a strong influence on maximal aerobic capacity (VO2max); thus, BFR exercise training could augment aerobic capacity when performed repeatedly. PURPOSE: To determine the impact of BFR during and following exercise on ventricular filling, hormone release, and training response. METHODS: Venous return was estimated via ultrasound measures of inferior vena cava diameter (IVCD) and end-diastolic volume (EDV) while participants (n = 13) had tourniquets inflated around their upper thigh during and following semi-recumbent cycling. Graded occlusion pressures were tested in each exercise condition to determine the greatest reduction in venous return and these pressures were used in two separate 2-week BFR training models: 1) BFR during walking (20 min) and 2) BFR following sprint cycling (5x10s). For both styles of BFR exercise, the hormonal response to a single training bout was analyzed using pre/post blood draws with VO2max measured before and after training. RESULTS: Compared to the control, BFR effectively reduced venous return during exercise at 100% arterial occlusion pressure (IVCD 15%; EDV 11%, both p < 0.05) and at 75% occlusion pressure during recovery (IVCD 20%; EDV 18%, both p < 0.02). Increased plasma renin and ADH concentrations were observed following exercise (pooled, p < 0.05) for BFR during walking (renin: 19.6 ± 9.4 to 40.8 ± 16.7 ng/L; ADH: 6.3 ± 4.1 to 28.5 ± 30.8 pmol/L) and post sprint exercise (renin: 24.2 ± 14.9 to 121 ± 72.7 ng/L; ADH:7.1 ± 3.4 to 374.1 ± 311 pmol/L). Following two weeks of training with BFR during walking, absolute VO2max improved (6.8 ± 6.4%) but was unchanged in the post exercise BFR model, with large inter-individual variability. CONCLUSION: Reducing venous return via leg BFR leads to increases in circulating blood-volume regulating hormones. Preliminary work suggests BFR during exercise results in greater changes in VO2max.

Neuroendocrine hormone status and diuretic response to atrial natriuretic peptide in patients with acute heart failure.

Given the various effects of sacubitril/valsartan in heart failure, a deeper understanding of atrial natriuretic peptide (ANP) actions is warranted. Natriuresis is a fundamental action of ANP in acute heart failure (AHF), whereas the diuretic effect of ANP is different in each patient according to the diversity of renal response to ANP, which is affected by baseline plasma ANP status and deficiency of circulating ANP. Meanwhile, associations between other neuroendocrine hormones and the diuretic response to ANP are unclear. This study investigated the impact of pivotal neuroendocrine hormones on the diuretic effects of exogenous ANP, carperitide. Plasma ANP, renin, aldosterone, and vasopressin levels and the diuretic effect of 0.0125μg/kg/min of carperitide alone for the first 6h were prospectively evaluated in 75 patients with AHF. Lower ANP levels were significantly associated with a greater diuretic response to exogenous ANP (r=-0.35, P=0.002). Additionally, higher vasopressin levels were significantly related to the poor diuretic effects of exogenous ANP (r=-0.54, P<0.001). Plasma ANP and vasopressin concentrations were not significantly correlated (r=0.19, P=0.10). Baseline systolic blood pressure, renal function, and prior use of loop diuretics did not predict the diuretic response to exogenous ANP, whereas vasopressin levels independently predicted a diuretic response to exogenous ANP (P<0.001), as well as lower plasma ANP levels (P=0.027). Vasopressin status was significantly associated with the diuretic response to exogenous ANP in AHF, independent of plasma ANP status. The results may provide a better understanding of the actions of sacubitril/valsartan.