AVP Levels Research Articles

BDNF levels are associated with autistic traits in the general population

Evidence supports the notion that autistic symptoms and behaviors should be regarded as dimensional traits. The present study aimed to investigate the role of vasopressin (AVP), brain-derived neurotrophic factor (BDNF) and oxytocin (OXT) as potential biochemical correlates of subclinical autistic traits in a cohort of healthy young adults. One hundred and fifty-three subjects (80 males, 73 females) were recruited. Participants completed the Autism Spectrum Quotient (AQ), a widely used measure for the identification of autistic traits in the general population. Additionally, blood samples were obtained from all participants at the same time of the day to control for circadian variation. We conducted a multiple regression analysis using the AQ score as the dependent variable and age, sex, AVP, BDNF and OXT levels as the independent variables. The model explained approximately the 22% of the variance of the AQ score. Among the parameters included in the analysis, only BDNF levels were independent predictors of AQ score.

Maternal separation affects expression of stress response genes and increases vulnerability to ethanol consumption.

IntroductionMaternal separation is an early life stress event associated with behavioral alterations and ethanol consumption. We aimed to expand the current understanding on the molecular mechanisms mediating the impact of postnatal stress on ethanol consumption.MethodsIn the first experiment (T1), some of the pups were separated from their mothers for 6 hr daily (Maternal Separation group ‐ MS), whereas the other pups remained in the cage with their respective mothers (Control group ‐ C). In the second experiment (T2), mice from both groups were subjected to the model of free‐choice between water and sucrose solution or between water and ethanol solution. Maternal behavior was assessed at the end of T1. At the end of both T1 and T2, pups were subjected to the light/dark box behavioral test and blood corticosterone concentrations were analyzed.ResultsOur maternal separation protocol led to intense maternal care and affected weight gain of the animals. The expression of stress response genes was altered with higher levels of Crh and Pomc being observed in the hypothalamus, and higher levels of Crhr1, Crhr2, Htr2a and lower levels of Nr3c1 and Htr1a being observed in the hippocampus after T1. At the end of T2, we observed higher levels of Avp and Pomc in the hypothalamus, and higher levels of Crhr1, Crhr2, Nr3c1, Slc6a4, Bdnf and lower levels of Htr1a in the hippocampus. Additionally, maternal separation increased vulnerability to ethanol consumption during adolescence and induced changes in anxiety/stress‐related behavior after T2. Furthermore, voluntary ethanol consumption attenuated stress response and modified expression of reward system genes: enhancing Drd1 and Drd2, and reducing Gabbr2 in the striatum.ConclusionMaternal separation induced behavioral changes and alterations in the expression of key genes involved in HPA axis and in the serotonergic and reward systems that are likely to increase vulnerability to ethanol consumption in adolescence. We demonstrated, for the first time, that ethanol consumption masked stress response by reducing the activity of the HPA axis and the serotonergic system, therefore, suggesting that adolescent mice from the MS group probably consumed ethanol for stress relieving purposes.

Chronic central oxytocin infusion impairs sociability in mandarin voles

Oxytocin (OT) has been reported to increase social contact, however some studies have related OT to reduced social contact, particularly with unfamiliar individuals. The underlying mechanisms of OT on social contact remain unclear. In this study, male mandarin vole (Microtus mandarinus), a socially monogamous rodent, was used as an animal model in which osmotic minipumps were used to intracerebroventricularly administer two dosages of OT or saline for 12 consecutive days. We examined the effect of long-term OT treatment on social behavior, anxiety levels, and levels of oxytocin, vasopressin (AVP) and dopamine (DA) receptors mRNA expression in the nucleus accumbens (NAcc), and medial amygdala (MeA). The data showed that chronic central OT infusion decreased social preference behavior (a reduction of preference for interacting with novel social stimulus relative to a novel object) concomitant to a reduction of OT receptors in the NAcc and MeA. We also found alterations in AVP and DA receptor levels in the NAcc and MeA after treatment with OT. Moreover, chronic central OT treatment did not affect levels of anxiety-related behavior in male voles. In conclusion, these results indicated that chronic OT treatment may differ from the treatment effects predicted in short-term studies, and significant dosage effects were observed.

Altered vasopressin and natriuretic peptide levels in a rat model of spinal cord injury: implications for the development of polyuria.

Urinary dysfunction is a common complaint following spinal cord injury (SCI) and is a leading issue for individuals with SCI that impacts their quality of life. One urinary complication that has received little attention is SCI-induced polyuria, even though individuals with SCI will significantly restrict their fluid intake to decrease urine production, leading to sequelae of medical complications. Understanding the mechanisms instigating the development of polyuria will allow us to target interventions that may alleviate polyuria symptoms, leading to significant improvements in the quality of life and urinary health of individuals with SCI. In a rat SCI contusion model, an increase in the amount of urine excreted over a 24-h period ( P ≤ 0.001) was found at 2 wk postinjury. The urine excreted was more dilute with decreased urinary creatinine and specific gravity ( P ≤ 0.001). Several factors important in fluid balance regulation, vasopressin (AVP), natriuretic peptides, and corticosterone (CORT), also changed significantly postinjury. AVP levels decreased ( P = 0.042), whereas atrial natriuretic peptide (ANP) and CORT increased ( P = 0.005 and P = 0.031, respectively) at 2 wk postinjury. There was also a positive correlation between the increase in ANP and urine volume postinjury ( P = 0.033). The changes in AVP, ANP, and CORT are conducive to producing polyuria, and the timing of these changes coincides with the development of SCI-induced polyuria. This study identifies several therapeutic targets that could be used to ameliorate polyuria symptoms and improve quality of life in individuals with SCI.

Arginine vasopressin, copeptin, and the development of relative AVP deficiency in hemorrhagic shock

BackgroundArginine vasopressin (AVP) is critical for maintaining vasomotor tone and low levels have been associated with the development of irreversible shock. We investigated the clinical relationship between AVP, copeptin (the C-terminal fragment of the AVP precursor), and the development of relative AVP deficiency following hemorrhagic shock. MethodsA prospective, observational study of 21 hypotensive (SBP<90 mmHg X 2) or presumptively bleeding trauma patients was conducted. Demographics, mechanism of injury, vital signs, laboratory values, transfusions, crystalloid volume, and blood samples were collected on arrival and serially for 48 h. AVP and copeptin were measured post hoc. ResultsAVP and copeptin levels were markedly elevated on admission, but decreased rapidly over time (p < 0.001). AVP and copeptin levels were positively correlated on admission (r = 0.769, p < 0.001), in the ICU (r = 0.768, p < 0.001), and at 48 h (r = 0.537, p = 0.02). Initial AVP and copeptin levels predicted the need for ≥10 unit blood product transfusion (AUC = 81% and 87%, respectively). The development of a relative AVP deficiency occurred frequently and was associated with an increased need for blood product transfusion. ConclusionCopeptin correlates well with AVP and initial values predict the need for massive transfusion in trauma patients. Copeptin demonstrates promise as a clinical biomarker in hemorrhagic shock.

563. Vasopressin (AVP) Gene Modulates Risk of Alcohol Dependence via Effects on Stress and Anxiety

Evidence suggests a role for AVP in addictive disorders given its ability to modulate stress responses and social interaction. In rats, elevated basal AVP levels are associated with increased alcohol consumption, while pharmacological antagonism of AVP receptors reduces alcohol consumption. AVP single nucleotide polymorphism (SNP) rs2282018 (A G) is associated with decreased AVP levels. We studied the relationship of rs2282018 to AD, and anxiety and stress responses that may mediate AD vulnerability.

Amphetamine treatment affects the extra‐hypothalamic vasopressinergic system in a sex‐ and nucleus‐dependent manner

The lateral septum (LS), a brain structure implicated in addictive behaviours, regulates the activation of dopaminergic neurones in the ventral tegmental area. Vasopressinergic projections from the extended amygdala to the LS, which are sexually dimorphic, could be responsible for the vulnerability to addiction in a sex-dependent manner. The present study aimed to investigate the modulatory effects of amphetamine (AMPH) on the expression of vasopressin (AVP) in the vasopressinergic extra-hypothalamic system in sensitised male and female rats. Adult male and female Sprague-Dawley rats underwent an AMPH-locomotor sensitisation protocol. Acute AMPH increased AVP mRNA expression in the medial amygdala (MeA), whereas AMPH-induced sensitisation increased AVP mRNA expression in the bed nucleus of the stria terminalis (BNST) only in females. Interestingly, the increase in AVP expression in BNST was higher in oestrus females compared to dioestrus females and acute AMPH resulted in a decrease in AVP levels in the LS, only in males. Thus, there are complex and region-specific interactions between AMPH and the extra-hypothalamic vasopressinergic system in the brain, underlying possible alterations in different behaviours caused by acute and chronic AMPH exposure.

Inhibition of neuronal nitric oxide synthase activity does not alter vasopressin secretion in septic rats.

During the early phase of sepsis, hypotension is accompanied by increase of plasma vasopressin hormone (AVP) levels, which decline during the late phase. This hypotension is due in part to increase of nitric oxide (NO) synthesis by nitric oxide synthase (NOS) enzyme. Neuronal isoform of this enzyme (nNOS) is present in vasopressinergics neurons of hypothalamus, but its role in vasopressin secretion during sepsis is unknown. We evaluated the role of nNOS in NO production and vasopressin secretion during sepsis. Wistar rats received 7-nitroindazole (50mg/kg, i.p.), an inhibitor of nNOS activity, or vehicle and were submitted to septic stimulus by cecal ligation and puncture (CLP). At the time points 0, 4, 6, 18 and 24h after sepsis induction the animals were decapitated and neurohypophysis and hypothalamus were removed for analysis of vasopressin content and NOS activity, respectively. Hematocrit, serum sodium, osmolality, proteins and plasmatic AVP were quantified. Mortality was not affected by 7-nitroindazole (7-NI). Sodium and plasma proteins levels decreased after CLP and the treatment anticipated the protein loss, and delayed serum sodium decrease. Septic animals treated with 7-NI showed decrease of osmolality 4h after CLP. Nitric oxide synthase activity in hypothalamus increased at 4 and 24h after CLP and was reduced with 7-NI. Neurohypophysis content of AVP diminished after CLP and 7-NI did not alter this parameter. Plasma AVP levels increased at 6h and decreased 18 and 24h after CLP. Treatment with 7-NI did not alter plasma vasopressin levels. We concluded that nNOS does not have a substantial role in vasopressin secretion during experimental sepsis.

Acute and chronic hyperglycemic effects of vasopressin in normal rats: involvement of V1A receptors.

Recent epidemiological studies have revealed novel relationships between low water intake or high vasopressin (AVP) and the risk of hyperglycemia and diabetes. AVP V1A and V1B receptors (R) are expressed in the liver and pancreatic islets, respectively. The present study was designed to determine the impact of different levels of circulating AVP on glucose homeostasis in normal Sprague-Dawley rats, as well as the respective roles of V1AR and V1BR. We showed that acute injection of AVP induces a dose-dependent increase in glycemia. Pretreatment with a selective V1AR antagonist, but not a V1BR antagonist, dose-dependently prevented the rise in glycemia. V1BR antagonism did not modify the hyperinsulinemic response, resulting from AVP-induced hyperglycemia, but enhanced the fall in glucagonemia. Acute administration of selective V1AR or V1BR agonists confirmed the involvement of V1AR in the hyperglycemic effect of AVP. In chronic experiments, AVP levels were altered in both directions. Sustained AVP infusion through implantable minipumps induced a time-dependent increase in fasting glycemia, whereas lowering endogenous AVP by increasing water intake had no effect. After 4 wk of AVP infusion, the rise in glycemia amounted to 1.1 mmol/l (P < 0.01) without significant change in insulinemia. This effect was attenuated by cotreatment with a V1AR antagonist. Similar results were observed in lean Zucker rats. These findings demonstrate for the first time a causal link between chronic high AVP and hyperglycemia through V1AR activation and, thus, provide a pathophysiological explanation for the relationship observed in human cohorts between the AVP-hydration axis and the risk of diabetes.

The Effect of Calcium and Available Phosphorus Levels on Performance, Egg Quality and Bone Characteristics of Japanese Quails at End of the Egg-Production Phase

Calcium (Ca) and available phosphorus (avP) requirements for egg production are different between the beginning and the end of the egg-production cycle. The objective of this study was to estimate the Ca and avP requirements of Japanese quails at end of the production phase. In total, 256 Japanese quails with 48 weeks of age were randomly distributed in 2 x 2 factorial arrangement consisting of two Ca levels (29 and 38 g/kg) and two avP levels (1.5 and 3.0 g/kg), totaling four treatments with eight replicates of eight hens each. The variables evaluated were feed intake (FI); egg production (EP); marketable egg production (MEP); egg weight (EW); egg mass (EM); feed conversion ratio per egg mass (FCRM); feed conversion ratio per dozen eggs (FCRD); livability (L); yolk weight (YW), albumen weight (AW), eggshell weight (SW); yolk percentage (YP), albumen percentage (AP), eggshell percentage (SP), specific egg weight (SEW); bone calcium percentage (BCa), bone phosphorus percentage (BP), bone ash weight (Bash) and bone ash percentage (PBash). There was no interaction between Ca and avP levels for any of the evaluated parameters, except for SEW. Quail performance was not influenced by the treatments, except for MEP. Bone characteristics were not influenced by the tested dietary Ca and avP levels. However, SW and SP increased and AP decreased as dietary Ca level increased. The dietary supplementation of 38 g Ca/kg and 3.0 g avP/kg may increase marketable egg production and the egg quality of Japanese quails at end of the production cycle.

Plasma copeptin as biomarker of disease progression and prognosis in cirrhosis

Research on vasopressin (AVP) in cirrhosis and its role in the assessment of prognosis has been hindered by the difficulty of measuring AVP levels accurately. Copeptin, a 39-aminoacid glycopeptide, is released from the neurohypophysis together with AVP. Copeptin could have a role as biomarker of prognosis in cirrhosis as it may reflect circulatory dysfunction. The aim of this study is to investigate the role of copeptin as biomarker of disease progression and prognosis in cirrhosis. This prospective study is divided in 2 study protocols including 321 consecutive patients. Plasma copeptin levels were measured in all patients at study inclusion. Protocol 1: to investigate the relationship of copeptin with kidney and circulatory function (56 patients). Protocol 2: to investigate the relationship between copeptin and prognosis, as assessed by the development of complications of cirrhosis or mortality at 3months (265 patients admitted to hospital for complications of cirrhosis). Patients with decompensated cirrhosis showed significantly higher plasma copeptin levels compared to those of patients with compensated cirrhosis. Copeptin levels had a significant positive correlation with model for end-satge liver disease (MELD) score, AVP, endogenous vasoconstrictor systems, and kidney function parameters. Patients developing complications of cirrhosis or mortality had significantly higher plasma copeptin levels compared to those of the remaining patients. Plasma copeptin levels were an independent predictive factor of both the development of complications and mortality at 3months. This was confirmed in a validation series of 120 patients. Copeptin is a novel biomarker of disease progression and prognosis in cirrhosis. Copeptin is a fragment of the vasopressin precursor, a hormone that is known to be increased in patients with cirrhosis and that plays a role in the development of complications of the disease. Vasopressin is difficult to measure, but copeptin is a more stable molecule and is easier to measure in blood. Solà and Kerbert and colleagues have shown in a series of 361 patients that copeptin is markedly increased in patients with cirrhosis who develop complications during the following 3months, compared to those patients who do not develop complications. Moreover, copeptin correlates with prognosis.

Angiotensin Type-2 Receptors Influence the Activity of Vasopressin Neurons in the Paraventricular Nucleus of the Hypothalamus in Male Mice.

It is known that angiotensin-II acts at its type-1 receptor to stimulate vasopressin (AVP) secretion, which may contribute to angiotensin-II-induced hypertension. Less well known is the impact of angiotensin type-2 receptor (AT2R) activation on these processes. Studies conducted in a transgenic AT2R enhanced green fluorescent protein reporter mouse revealed that although AT2R are not themselves localized to AVP neurons within the paraventricular nucleus of the hypothalamus (PVN), they are localized to neurons that extend processes into the PVN. In the present set of studies, we set out to characterize the origin, phenotype, and function of nerve terminals within the PVN that arise from AT2R-enhanced green fluorescent protein-positive neurons and synapse onto AVP neurons. Initial experiments combined genetic and neuroanatomical techniques to determine that γ-aminobutyric acid (GABA)ergic neurons derived from the peri-PVN area containing AT2R make appositions onto AVP neurons within the PVN, thereby positioning AT2R to negatively regulate neuroendocrine secretion. Subsequent patch-clamp electrophysiological experiments revealed that selective activation of AT2R in the peri-PVN area using compound 21 facilitates inhibitory (ie, GABAergic) neurotransmission and leads to reduced activity of AVP neurons within the PVN. Final experiments determined the functional impact of AT2R activation by testing the effects of compound 21 on plasma AVP levels. Collectively, these experiments revealed that AT2R expressing neurons make GABAergic synapses onto AVP neurons that inhibit AVP neuronal activity and suppress baseline systemic AVP levels. These findings have direct implications in the targeting of AT2R for disorders of AVP secretion and also for the alleviation of high blood pressure.

Available phosphorus levels in diets supplemented with phytase for male broilers aged 22 to 42 days kept in a high-temperature environment

This study was conducted to evaluate the effect of reduction of the available phosphorus (avP) in diets supplemented with 500 FTU/kg phytase on performance, carcass characteristics, and bone mineralization of broilers aged 22 to 42 days kept in a high-temperature environment. A total of 336 Cobb broilers with an average initial weight of 0.883±0.005 kg were distributed in a completely randomized design with six treatments - a positive control (0.354 and 0.309% avP without addition of bacterial phytase for the phases of 22 to 33 and 34 to 42 days, respectively), and another five diets with inclusion of phytase (500 FTU) and reduction of the level of avP (0.354, 0.294, 0.233, 0.173, and 0.112%; and 0.309, 0.258, 0.207, 0.156, and 0.106% for the phases of 22 to 33 and 34 to 42 days, respectively) - eight replicates, and seven birds per cage. The experimental diets were formulated to meet all nutritional requirements, except for avP and calcium. Birds were kept in climatic chambers at a temperature of 32.2±0.4 °C and air humidity of 65.3±5.9%. Phytase acted by making the phytate P available in diets with reduction in the levels of avP, keeping feed intake, weight gain, feed:gain, and carcass characteristics unchanged. Treatments affected ash and calcium deposition and the Ca:P ratio in the bone; the group fed the diets with 0.112 and 0.106%, from 22 to 33 and 34 to 42 days of age, respectively, obtained the lowest values, although the phosphorus deposition in the bone was not affected. Diets supplemented with 500 FTU of phytase, with available phosphorus reduced to 0.173 and 0.156%, and a fixed Ca:avP ratio of 2.1:1, meet the requirements of broilers aged 22 to 33 and 34 to 42 days, respectively, reared in a high-temperature environment.

The type-1 cannabinoid receptor modulates the hydroelectrolytic balance independently of the energy homeostasis during salt load

Hydroelectrolytic imbalances, such as saline load (SL), trigger behavioral and neuroendocrine responses, such as thirst, hypophagia, vasopressin (AVP) and oxytocin (OT) release and hypothalamus–pituitary–adrenal (HPA) axis activation. To investigate the participation of the type-1 cannabinoid receptor (CB1R) in these homeostatic mechanisms, male adult Wistar rats were subjected to SL (0.3M NaCl) for four days. SL induced not only increases in the water intake and plasma levels of AVP, OT and corticosterone, as previously described, but also increases in CB1R expression in the lamina terminalis, which integrates sensory afferents, as well as in the hypothalamus, the main integrative and effector area controlling hydroelectrolytic homeostasis. A more detailed analysis revealed that CB1R-positive terminals are in close apposition with not only axons but also dendrites and secretory granules of magnocellular neurons, particularly vasopressinergic cells. In satiated and euhydrated animals, the intracerebroventricular administration of the CB1R selective agonist ACEA (0.1μg/5μL) promoted hyperphagia, but this treatment did not reverse the hyperosmolality-induced hypophagia in the SL group. Furthermore, ACEA pretreatment potentiated water intake in the SL animals during rehydration as well as enhanced the corticosterone release and prevented the increase in AVP and OT secretion induced by SL. The same parameters were not changed by ACEA in the animals whose daily food intake was matched to that of the SL group (Pair-Fed). These data indicate that CB1Rs modulate the hydroelectrolytic balance independently of the food intake during sustained hyperosmolality and hypovolemia.

The secretion patterns and roles of cardiac and circulating arginine vasopressin during the development of heart failure

ObjectiveThe aim of this study is to investigate local cardiac and circulating AVP secretion during heart failure and to determine whether AVP mediates ventricular remodeling. MethodsWe assessed cardiac function and AVP levels of post-myocardial infarction (MI) heart-failure rats 3 weeks (n = 10), 4 weeks (n = 10), 6 weeks (n = 10), 9 weeks (n = 15) after the proximal left anterior descending coronary artery (LAD) ligation. Ten sham-operated rats were used as the control group. In vitro, cardiac microvascular endothelial cells (CMECs) were initiated from isolated Wistar rat hearts and subjected to Ang II to induce AVP expression and secretion. Besides, the effects of AVP stimulation on CMECs and cardiac fibroblasts (CFs) were studied using methylthiazol tetrazolium assay, Western blotting and real-time PCR. ResultsWith cardiac dysfunction, plasma and local cardiac AVP, aldosterone levels increased over time, peaking at 9 weeks post-MI. AVP levels were negatively correlated with serum Na+ and LVEF but positively correlated with LVEDD and myocardial hydroxyproline. In CMECs treated with Ang II, AVP mRNA and protein expression increased. In addition, AVP promoted CFs proliferation and up-regulated the expression of endothelin-1 and connective tissue growth factor. ConclusionCMECs are the cellular sources of elevated local heart AVP stimulated with Ang II/AT1. An intrinsic cardiac AVP system exists. Local cardiac and circulating AVP secretion were enhanced by deteriorating cardiac function. AVP may promote ventricular remodeling. Thus, AVP could be an important mediator of myocardial fibrosis in late-stage heart failure.

Modulation of the activity of vasopressinergic neurons by estrogen in rats refed with normal or sodium-free food after fasting

Feeding increases plasma osmolality and ovarian steroids may influence the balance of fluids. Vasopressin (AVP) neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) express estrogen receptor type β (ERβ), but not estrogen receptor type α (ERα). The circumventricular organs express ERα and project efferent fibers to the PVN and SON. Our aim was to assess whether interactions exist between food state-related osmolality changes and the action of estrogen on AVP neuron activity and estrogen receptor expression. We assessed plasma osmolality and AVP levels; fos-coded protein (FOS)- and AVP-immunoreactivity (-IR) and FOS-IR and ERα-IR in the median preoptic nucleus (MnPO) and organ vasculosum lamina terminalis (OVLT) in estrogen-primed and unprimed ovariectomized rats under the provision of ad libitum food, 48h of fasting, and subsequent refeeding with standard chow or sodium-free food. Refeeding with standard chow increased plasma osmolality and AVP as well as the co-expression of FOS-IR/AVP-IR in the PVN and SON. These responses were not altered by estrogen, with the exception of the decreases in FOS-IR/AVP-IR in the lateral PVN. During refeeding, estrogen modulates only a subpopulation of AVP neurons in the lateral PVN. FOS-ERα co-expression in the ventral median preoptic nucleus (vMnPO) was reduced by estrogen and increased after refeeding with standard chow following fasting.It appears that estrogen may indirectly modulate the activity of AVP neurons, which are involved in the mechanism affected by hyperosmolality-induced refeeding after fasting. This indirect action of estrogen can be at least in part via ERα in the vMnPO.

Ghrelin effects expression of several genes associated with depression-like behavior.

Ghrelin (Ghr) is an orexigenic peptide that is being investigated for its potential role in development of anxiety-like behavior and modulation of depressive-like symptoms induced by bilateral olfactory bulbectomy (OB) in rodents. Olfactory bulbectomy is an animal model useful to study of depression and Ghr could be an alternative therapeutic tool in depression therapy. We studied the effects of intracerebroventricular (i.c.v.) Ghr administration on the expression of hypothalamic genes related to depression and mood (delta opioid receptor (DOR), mu opioid receptor (MOR) and kappa opioid receptor (KOR), lutropin-choriogonadotropic hormone receptor (LHCGR), serotonin transporter (SERT), interleukin 1 beta (IL-1b), vasopressin (AVP) and corticotrophin releasing hormone (CRH)) in OB animals, as well as changes in plasma levels of AVP, CRH and adenocorticotropic hormone (ACTH). We found that acute Ghr 0.3 nmol/μl administration increases gene expression of DOR, SERT and LHCGR in OB mice and decreased expression of IL-1b, suggesting that these genes could be involved in the antidepressant-like effects of Ghr. In addition, OB animals exhibit high AVP gene expression and elevated plasma concentrations of AVP and ACTH and acute Ghr 0.3 nmol/μl administration reduces AVP gene expression and the concentration of these hormones, suggesting that peptide-effects on depressive-like behavior could be mediated at least in part via AVP. In conclusion, this study provides new evidence about genes, receptors and hormones involved in the antidepressant mechanism/s induced by Ghr in OB animals.

Abstract 033: Novel Neurohumoral Responses to Head Upright Tilt Testing in Children with Chronic Nausea and Orthostatic Intolerance

Children with chronic unexplained nausea have a high incidence of orthostatic intolerance (OI), with exaggerated suppression of baroreflexes upon standing. The renin-angiotensin system (RAS) is known to play a role in disorders related to OI likely as a compensatory mechanism for CV regulation. The objective of this study was to characterize the neurohumoral response to head upright tilt testing (HUT) in children with chronic nausea and OI. Forty-eight patients (mean age [range] of 15 [10-18] years)(36 females, 12 males) completed HUT. GI symptoms including nausea were reported during HUT. Subjects were maintained supine for 15 min before 45 min 70° HUT. Plasma hormones catecholamines (Cat), epinephrine (Epi), norepinephrine (NE), vasopressin (AVP), aldosterone (Aldo), renin, and angiotensins [Ang-(1-7) and AngII] were measured in blood sampled immediately before and after 15 min of upright tilt. Of the 48 HUTs, 35 subjects demonstrated OI. There were no differences in supine blood pressures (BP) or humoral measures between groups. OI subjects had lower systolic (105 ± 4 vs. 127 ± 4 mm Hg, p=0.001), diastolic (61 ± 2 vs. 77 ± 2, p&lt;0.0001), and mean arterial (76 ± 2 vs. 93 ± 2, p=0.0002) BPs during HUT compared to normal subjects (mean ± SEM). They also had higher Cat (625 ±44 vs. 466 ± 61 pg/ml, p=0.02), AngII (48 ± 3 vs. 35 ± 4 pg/ml, p=0.04), and AVP (46 ± 12 vs. 18 ± 14 pg/ml, p=0.01) during HUT compared to non-OI subjects. There was a negative correlation between Ang-(1-7) and NE at baseline (r=-0.6, p&lt;0.05) and HUT (r=-0.6, p=0.03) in Non-OI subjects that was not seen in OI subjects. Nausea was reproduced by HUT in 42% (20 of 48) of this cohort. Nausea subjects did not have a change in DBP (61 ± 2 vs. 61 ± 3 mm Hg) upon tilt, but had significantly higher AVP (72 ± 20 pg/ml, p=0.01) during HUT compared to subjects who did not experience nausea (15 ± 7, p=0.001). Children with chronic nausea testing positive for OI have elevated Cat, AngII, and AVP levels upon HUT. Elevated serum AVP may be a key trigger to nausea with orthostatic challenge independent of OI on HUT. In addition to this humoral response, the absence of change in DBP upon standing suggests a failure in both the sympathetic nervous system and RAS compensatory mechanisms necessary to sustain HUT in children with chronic nausea and OI.

Influence of phytate level on broiler performance and the efficacy of 2 microbial phytases from 0 to 21 days of age

Phytate is an antinutrient in animal feeds, reducing the availability and increasing the excretion of nutrients. Phytases are widely used to mitigate the negative influences of phytate. This trial was designed to compare the efficacy of 2 Escherichia coli-derived phytases on broiler performance and bone ash as influenced by dietary phytate level. A total of 1,024 Arbor Acres male broilers were used with 8 replicate pens of 16 birds/pen. Experimental diets were based on low available phosphorus (avP; 1.8 g/kg) with low (6.40 g/kg) or high (10.65 g/kg) phytate. The low-avP diets were then supplemented with mono-dicalcium phosphate to increase the avP level to 4.5 g/kg, 500 phytase units/kg of phytase A, or 500 phytase units/kg of phytase B to create 8 experimental diets. Feed intake, BW gain, FCR, and livability were influenced by a P source × phytase interaction. Feed intake, BW gain, and livability were reduced and FCR was higher in broilers fed low-avP diets, particularly in the presence of high phytate. Phytase A or phytase B improved feed intake, BW gain, and FCR, particularly in the high-phytate diet. However, broilers fed phytase A ate more and were heavier than broilers fed phytase B. Tibia ash was lowest in broilers fed the low-avP diet and highest in broilers fed the diet supplemented with mono-dicalcium phosphate. Phytase increased tibia ash, and broilers fed phytase A had an increase in tibia ash compared with broilers fed phytase B. In conclusion, high dietary phytate reduced broiler performance. Phytase A and phytase B improved bone ash and growth performance, especially in the high-phytate diets. However, phytase A was more efficacious than phytase B, regardless of the level of phytate.

Central administration of IL‐1 receptor antagonist increases vasopressin secretion in late phase of sepsis in rats (876.7)

Clinical and experimental studies have reported that the initial phase of sepsis is characterized by elevated plasma vasopressin (AVP) concentrations. However, in the late phase, despite of the significant decrease in the arterial pressure, the AVP secretion decrease and the plasma concentrations remain unusually low, contributing to the hypotension, vasodilator shock, and death. Considering the role of AVP in the vasopressor response, the elucidation of the mechanisms of this deficient hormone secretion may contribute to therapy during sepsis.The aim of this study was to analyze the effect of IL‐1ra (an Interleukin‐1 receptor antagonist) on sepsis‐induced alterations in plasma AVP and NO, and cerebrospinal fluid (CSF) NO levels. After Wistar rats were intracerebroventricullary injected with 2 ul of IL‐1ra (9 nmol/ or vehicle (PBS 0.01M) sepsis was induced by cecal ligation and puncture (CLP). Blood samples were collected from different groups of rats (n=6‐8/group) by decapitation after 4‐, 6‐ and 24‐h. Specific ELISA and Chemiluminescence assays were used for measurement of AVP and NO concentrations, respectively. All experiments were carried out according to an institutional ethical committee approved protocol.IL‐1ra administration did not alter plasma vasopressin after 4‐ and 6‐h as compared to vehicle in CLP animals. In contrast, after 24‐h AVP levels were significantly (P&lt;0.01) higher in IL‐1ra treated animals as compared to vehicle treated animals. IL‐1ra administration significantly (P&lt;0.01) decreased NO concentration in CSF but not in plasma. Moreover, the survival rate of IL‐1ra treated rats increased by 38% in comparison to vehicle administered animals.In conclusion, the central administration of IL‐1ra increases AVP secretion in the late phase of sepsis which was beneficial for survival. We believe that one of the mechanisms for this effect of IL‐1ra is through reduction of NO concentration in CSF of the septic rats.