Injection Of Arginine Vasopressin Research Articles

Atrial Natriuretic Peptide Alleviates Motion Sickness Potentially through Regulating Endolymph Volume in the Inner Ear Increased by Arginine Vasopressin

Introduction: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aimed to investigate the anti-motion sickness action and inner ear-related mechanisms of atrial natriuretic peptide (ANP). Methods: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. Results: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. Conclusion: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.

Contrasting central and systemic effects of arginine-vasopressin on urinary marking behavior as a social signal in male mice

Arginine-vasopressin (AVP) is a neurohypophyseal peptide that plays a critical role in the regulation of social behavior in mammals. Neuronal AVP regulates male-specific social signaling processes, such as exocrine urinary scent deposition and marking behavior in mice. In the periphery, AVP is transported to the portal bloodstream and acts as an antidiuretic hormone. These AVP dynamics imply that the central role of AVP in the stimulation of urinary marking is dissociated with the peripheral role of AVP in the retention of osmotic conditions. Using male BALB/c mice as subjects, peripheral injection of AVP decreased urinary marking and urination. In contrast, a central infusion of AVP facilitated urinary marking with no effect on urination, while an antagonist of the AVP 1a receptor inhibited marking. Centrally AVP-injected mice also exhibited typical behaviors, such as hiccough/sneeze-like reactions and flash scratching, particularly when confronted with a stimulus mouse through a wire mesh screen. Significant expression of these typical reactions in these mice resulted in the disruption of marking deposition. Further analysis of AVP synthesis illustrated that AVP levels increased in the midbrain but not in the circulation immediately after the test, particularly when confronted with a stimulus mouse. The central AVP regulates urinary marking and other typical behaviors in a dose- and situation-dependent manner. The sequential process implies that centrally synthesized AVP may be secreted into the circulation following immediate neuronal processes, and then peripheral AVP acts as an antidiuretic hormone on urinary marking behavior.

Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes.

Insulin-induced hypoglycemia is a major treatment barrier in type-1 diabetes (T1D). Accordingly, it is important that we understand the mechanisms regulating the circulating levels of glucagon. Varying glucose over the range of concentrations that occur physiologically between the fed and fuel-deprived states (8 to 4 mM) has no significant effect on glucagon secretion in the perfused mouse pancreas or in isolated mouse islets (in vitro), and yet associates with dramatic increases in plasma glucagon. The identity of the systemic factor(s) that elevates circulating glucagon remains unknown. Here, we show that arginine-vasopressin (AVP), secreted from the posterior pituitary, stimulates glucagon secretion. Alpha-cells express high levels of the vasopressin 1b receptor (V1bR) gene (Avpr1b). Activation of AVP neurons in vivo increased circulating copeptin (the C-terminal segment of the AVP precursor peptide) and increased blood glucose; effects blocked by pharmacological antagonism of either the glucagon receptor or V1bR. AVP also mediates the stimulatory effects of hypoglycemia produced by exogenous insulin and 2-deoxy-D-glucose on glucagon secretion. We show that the A1/C1 neurons of the medulla oblongata drive AVP neuron activation in response to insulin-induced hypoglycemia. AVP injection increased cytoplasmic Ca2+ in alpha-cells (implanted into the anterior chamber of the eye) and glucagon release. Hypoglycemia also increases circulating levels of AVP/copeptin in humans and this hormone stimulates glucagon secretion from human islets. In patients with T1D, hypoglycemia failed to increase both copeptin and glucagon. These findings suggest that AVP is a physiological systemic regulator of glucagon secretion and that this mechanism becomes impaired in T1D.

The Role of Arginine Vasopressin in Modulating Inspiratory Bursting Behavior in the Hypoglossal Motor Nucleus in Neonatal Mice

Arginine vasopressin (AVP) is classically known as a hormone, but it also acts as a neurotransmitter that binds V1a receptors in the central nervous system. V1a receptors are expressed at high levels early in postnatal life in cranial and spinal motoneurons. While AVP receptor expression levels decrease in some cranial motoneuron populations with increasing developmental age, AVP receptor mRNA levels are expressed at high levels in the hypoglossal (XII) motor nucleus in adult mice. Recordings from individual XII motoneurons demonstrated that AVP has excitatory effects on young XII motoneurons, although the signaling pathways and effector ion channels remain to be fully elucidated. Additionally, previous research demonstrated that GABAergic disinhibition within the paraventricular nucleus of adult male rats, which has the effect of promoting AVP release, led to stimulation of breathing and increased diaphragm and genioglossus (innervated by XII, primary tongue protruder) muscle activity. Whether AVP acts directly at XII motoneurons to potentiate inspiratory bursting is unknown. Our aim was to characterize the effects of AVP on inspiratory bursting behavior at XII motoneurons. To test our hypothesis that AVP will potentiate inspiratory bursting behavior, we utilized an in vitro medullary brainstem slice (600 µM) preparation of neonatal (postnatal day, P0-5) CD1 mouse brains of either sex that contains the nuclei for respiratory movement of the tongue. By superfusing the slice with warmed artificial cerebral spinal fluid, we were able to record inspiratory bursting activity using a suction electrode under baseline conditions and in response to local drug application. Local injections of AVP at 0.01 µM had little effect on inspiratory bursting amplitude (111% ± 3% of baseline, n=6), but at 0.1 µM or 1 µM, initial results suggest it increased inspiratory burst amplitude (134% ± 5% of baseline, n=13 and 130% ± 8% of baseline, n=7 respectively, p = 0.0889). The excitatory effect of AVP was significantly diminished using a V1a receptor antagonist, d(CH2)51Tyr(Me)2Arg8) Vasopressin (500nM) (Initial AVP increase in burst amplitude: 141% ± 8%; AVP after antagonist: 113% ± 4%; AVP after washout: 120% ± 3%, n=10, p = 0.0437). Vasopressin and oxytocin are closely related nonapeptides, and since the XII motor nucleus also expresses oxytocin receptors, we next tested whether the AVP effects could be attributed to activation of the oxytocin receptor. Our preliminary results suggest that the oxytocin receptor antagonist, L-371,257 (50nM), did attenuate the response of AVP (Initial AVP increase in burst amplitude: 144% ± 11%; AVP after antagonist: 114% ± 5%; AVP after Washout: 122% ± 6%, n=8, p = 0.0901). Lastly, we discovered that vasopressin-related potentiation of inspiratory burst amplitude has an age-dependent increase from P0-5 (regression fit: y=13.933x+12.401, R2=0.4411, p=0.000402). Our results indicate that vasopressin, acting at V1a, and possibly oxytocin, receptors, can potentiate XII inspiratory bursting behavior in neonatal mice. Whether vasopressin has a role in maintaining airway patency in vivo in adult animals will need to be addressed in future studies.

Postnatal AVP treatments prevent social deficit in adolescence of valproic acid-induced rat autism model

Studies have shown that arginine-vasopressin (AVP) is an important neuropeptide regulating social behaviors. The present work aimed to detect changes in the AVP numbers and level in a valproic acid (VPA)-induced rat model of autism and the underlying mechanism of its pathogenesis. Our results indicated that infants exposed to VPA showed obviously impaired communication and repetitive behaviors with reduced number of AVP-ir cells in paraventricular nucleus (PVN) and cerebrospinal fluid (CSF). The postnatal subcutaneous injection of AVP can alleviate social preference deficits and stereotyped behaviors, accompanied with the increase of the AVP concentrations in the CSF. We concluded that AVP system was involved in etiology of VPA-induced autism-like symptoms and postnatal AVP treatment rescued the behavioral deficits,which could be a promising treatment for autism.

Inner Ear Arginine Vasopressin-Vasopressin Receptor 2-Aquaporin 2 Signaling Pathway Is Involved in the Induction of Motion Sickness

It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling. Vestibular training, V2R antagonist mozavaptan, or PKA inhibitor H89 blunted these changes in the V2R-AQP2 pathway signaling while reducing rotatory stimulus- or DDAVP (a V2R agonist)-induced motion sickness in rats and dogs. Therefore, our results suggest that activation of the inner ear AVP-V2R-AQP2 signaling pathway is potentially involved in the development of motion sickness; thus, mozavaptan targeting AVP V2Rs in the inner ear may provide us with a new application option to reduce motion sickness. SIGNIFICANCE STATEMENT: Motion sickness affects many people traveling or working. In the present study our results showed that activation of the inner ear arginine vasopressin-vaspopressin receptor 2 (V2R)-aquaporin 2 signaling pathway was potentially involved in the development of motion sickness and that blocking V2R with mozavaptan, a V2R antagonist, was much more effective in reducing motion sickness in both rat and dog; therefore, we demonstrated a new mechanism to underlie motion sickness and a new candidate drug to reduce motion sickness.

Effects of electroacupuncture on cochlear morphology and expression of aquaporins in rats with AVP-induced endolymphatic hydrops

ObjectiveThe objective of this study was to investigate the effects of EA on EH and the regulation of AQP2 and AQP7 protein expression in rats. MethodsTwenty-four rats were allocated randomly to four groups of blank group, EH group, EH + tolvaptan group and EH + EA group (n = 6 per group). EH rat model was established by intraperitoneally injection of arginine vasopressin (AVP). EA was administered at acupoints “Baihui (百会 GV 20)” and “Tinggong (听宫 SI 19)”. Rats in the EH + tolvaptan group and EH + EA group were treated with tolvaptan and EA, respectively, after EH establishment. Hematoxylin-eosin staining was used to measure the cochlear hydrops degree, and then the ratio of scala media (SM) area to SM + scala vestibuli (SV) area (R value) was calculated. Immunohistochemical method was used to observe AQP2/AQP7 protein expression in the rat cochlear lateral wall after treatment. Results①There was no endolymphatic hydrops in the blank group. Reissner’ s membrane was extended markedly and bulged into SV in cochleae of the EH group and endolymphatic hydrops was noted. Statistical analysis revealed that R value in the EH group showed a significant increase compared with that in the blank group (0.42 ± 0.02 vs. 0.31 ± 0.05, P = 0.000). The distension of Reissner's membrane was less obvious in the EH + tolvaptan group and EH + EA group when compared with the EH group. R value in the EH + tolvaptan group and the EH + EA group was significantly less than that in EH group (0.32 ±0.04 vs. 0.42 ± 0.02, P = 0.001;0.35 ± 0.05 vs. 0.42 ± 0.02, P = 0.012). The degree of the hydrops in the EH + EA group was not different from that in the EH + tolvaptan group (0.35 ± 0.05 vs. 0.32 ±0.04, P = 1.000). ②The AQP2 protein expression in the rat cochlear lateral wall of EH group was significantly increased when compared with the blank group (12.74 ± 5.18 vs. 5.92 ± 1.52, P = 0.014). The AQP2 protein expression in the rat cochlear lateral wall of EH + tolvaptan group and EH + EA group were all lower than that of the EH group (6.52 ± 2.73 vs. 12.74 ± 5.18, P = 0.029;6.95 ± 3.10 vs. 12.74 ± 5.18, P = 0.047). The AQP2 protein expression in the rat cochlear lateral wall of EH + EA group was not different from that in the EH + tolvaptan group (6.95 ± 3.10 vs. 6.52 ± 2.73, P = 1.000). ③The AQP7 protein expression in the rat cochlear lateral wall of EH group was significantly increased when compared with the blank group (30.32 ± 6.39 vs 16.64 ± 3.21, P = 0.000). The AQP7 protein expression in the rat cochlear lateral wall of EH + tolvaptan group and EH + EA group were all lower than that of the EH group (18.32 ± 2.45 vs. 30.32 ± 6.39, P = 0.001;19.54 ± 4.61 vs. 30.32 ± 6.39, P = 0.003). The AQP7 protein expression in the rat cochlear lateral wall of EH + EA group was not different from that in the EH + tolvaptan group (19.54 ± 4.61 vs. 18.32 ± 2.45, P = 1.000). ConclusionsThese results indicate that repeated EA stimulation exerted the same effects as tolvaptan application on AQPs levels and subsequent aquaretic effects. And dehydrating effect of EA on the inner ear might be associated with its down-regulation of both AQP2 and AQP7 protein expression, thereby provide a potential molecular mechanism involved in the treatment of Meniere's disease by EA.

Correlation between Urinary Excretion of Arginine-Vasopressin and Renal Reabsorption of Sodium and Water.

We developed an approach for quantitative assay of injected vasopressin in urine samples by ELISA under conditions of physiological suppression of hormone secretion from the neurohypophysis into the blood. In experiments on unanesthetized rats, water load (5 ml/100 g body weight) almost completely blocked secretion of arginine-vasopressin. Injection of arginine-vasopressin in a dose of 0.1 nmol/100 g body weight after water load enhanced reabsorption of solute-free water and renal excretion of Na+, K+, and Mg2+ by 13.3, 5.5, and 5.0 times, respectively; urinary excretion of Ca2+ remained unchanged. It was found that urinary excretion of arginine-vasopressin directly correlated with reabsorption of solute-free water and renal sodium excretion.

Effect of Vasopressin V1b Receptor Blockade on Activity of the Hypothalamic-Pituitary-Adrenal Axis in Old Monkeys with Depression-Like and Anxious Behavior Subjected to Stress or Injected with Vasopressin.

The effect of selective antagonist of the arginine vasopressin (AVP) V1b receptors on the secretion of ACTH and corticosteroids in response to insulin-induced hypoglycemia and injection of AVP is studied in old Macaca mulatta females with depression-like and anxious behavior. Intravenous antagonist in a dose of 1.1-1.7 μg/kg inhibits the increase of ACTH concentration, induced by hypoglycemia or injection of AVP. The degree of increase in the concentrations of hydrocortisone and dehydroepiandrosterone sulfate has not changed or increased. The effects of AVP antagonist prove that previously detected disorders in the reaction of the hypothalamic-pituitary-adrenal system in old Macaca mulatta with depression-like and anxious behavior could be caused by excessive activation of vasopressin V1b receptors on the pituitary corticotrophs, while the use of V1b receptor antagonists seems to be a promising method for prevention of these disorders.

Arginine Vasopressin-Aquaporin-2 Pathway-Mediated Dehydration Effects of Electroacupuncture in Guinea Pig Model of AVP-Induced Eendolymphatic Hydrops

To investigate the effects of electroacupuncture (EA) on endolymphatic hydrops (EH) and the regulation of arginine vasopressin (AVP)-aquaporin-2 (AQP2) pathway in guinea pigs. EH was induced in male guinea pigs by an intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui (GV 20) and Tinggong (SI 19) acupoints, once per day for 10 consecutive days. In histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin-eosin (HE) staining, and then the ratio of scala media (SM) area to SM + scala vestibuli (SV) area (R value) was calculated. In mechanical studies, a comparison of plasma AVP (p-AVP) concentrations, cyclic adenosine monophosphate (cAMP) levels, vasopressin type 2 receptor (V2R) and AQP2 mRNA expressions in the cochlea were compared among groups. EA significantly reduced cochlear hydrops in guinea pigs (P=0.001). EA significantly attenuated the AVPinduced up-regulation of p-AVP concentrations (P=0.006), cochlear cAMP levels (P=0.003) and AQP2 mRNA expression (P=0.016), and up-regulated the expression of V2R mRNA (P=0.004) in the cochlea. The dehydrating effect of EA might be associated with its inhibition of AVP-AQP2 pathway activation.

Regulation of Pulsatile and Entropic ACTH Secretion Under Fixed Exogenous Secretagogue Clamps.

Adrenocorticotropic hormone (ACTH) secretion is controlled by unobservable hypothalamic corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) pulses. Clamping exogenous CRH or AVP input could allow indirect quantification of the impact of the endogenous heterotypic hormone. We conducted a randomized, double-blind, placebo-controlled, crossover study in 28 healthy adults (16 men). Volunteers underwent a sex-steroid clamp and a cortisol clamp. ACTH was measured over 10 hours by 10-minute sampling during each of four randomized intravenous (IV) secretagogue clamps (i.e., continuous IV CRH, AVP, both peptides, or saline). Desensitization was tested by bolus injection of the noninfused peptide. Mean ± standard error of the mean 10-hour ACTH concentrations (ng/L) in the sex-combined analysis were: saline, 32 ± 4.6; AVP, 29 ± 4.6; CRH, 67 ± 6.2; and CRH-AVP, 67 ± 8.8 (any CRH vs AVP or saline, P < 0.0001). CRH and AVP increased approximate entropy (relative randomness) of ACTH release (P < 0.0001). Bolus AVP injection after CRH infusion yielded a 2.5-hour ACTH concentration of 46 ± 4.3, exceeding that seen after bolus CRH or saline injection (26 ± 3.3 and 24 ± 3.6, respectively; P = 0.002 and 0.001). Sex hormone clamps did not influence ACTH levels. A CRH, but not AVP, clamp yields sustained pulsatile ACTH secretion with high ACTH secretory-burst mass and randomness. After 10-hour CRH infusion, bolus AVP but not CRH, evoked marked ACTH release, likely caused by heterotypic sensitization of corticotropes by CRH. Similar interactions might underlie chronic stress states.

Effect of Endogenous Arginine-Vasopressin Arising from the Paraventricular Nucleus on Learning and Memory Functions in Vascular Dementia Model Rats.

The hippocampus is a key structure for encoding and processing memory and for spatial orientation, which are among the cognitive functions most sensitive to cerebral ischemia, hypoxia, and vascular dementia (VD). Since hippocampal formation is one of the principle forebrain targets for arginine-vasopressin (AVP) innervations arising in the hypothalamic paraventricular nucleus (PVN), we explored the contributions of AVP to VD pathogenesis. To this end, we randomly assigned pathogen-free, male Wistar rats to one of seven groups in a VD model and tested AVP treatment effects on spatial learning and memory using the Morris water maze. We also measured the superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration in brain samples and monitored the expression of AVP-positive neurons in the hippocampus by immunohistochemistry. The VD model with repeated cerebral ischemia-reperfusion injury evoked impairment of cognitive function and reduced cerebral concentrations of the antioxidation markers. Lesioning the rat PVN showed a similar effect on learning and memory and reduced antioxidation markers in the brain tissue. However, AVP injection into the PVN improved cognitive performance in VD rats, while enhancing/rectifying the changes in antioxidation markers. We conclude that our VD model may decrease AVP secretion in the PVN and subsequently reduce antioxidant capacity in the hippocampus, leading to impaired cognitive function.

Serotonin and arginine–vasopressin mediate sex differences in the regulation of dominance and aggression by the social brain

There are profound sex differences in the incidence of many psychiatric disorders. Although these disorders are frequently linked to social stress and to deficits in social engagement, little is known about sex differences in the neural mechanisms that underlie these phenomena. Phenotypes characterized by dominance, competitive aggression, and active coping strategies appear to be more resilient to psychiatric disorders such as posttraumatic stress disorder (PTSD) compared with those characterized by subordinate status and the lack of aggressiveness. Here, we report that serotonin (5-HT) and arginine-vasopressin (AVP) act in opposite ways in the hypothalamus to regulate dominance and aggression in females and males. Hypothalamic injection of a 5-HT1a agonist stimulated aggression in female hamsters and inhibited aggression in males, whereas injection of AVP inhibited aggression in females and stimulated aggression in males. Striking sex differences were also identified in the neural mechanisms regulating dominance. Acquisition of dominance was associated with activation of 5-HT neurons within the dorsal raphe in females and activation of hypothalamic AVP neurons in males. These data strongly indicate that there are fundamental sex differences in the neural regulation of dominance and aggression. Further, because systemically administered fluoxetine increased aggression in females and substantially reduced aggression in males, there may be substantial gender differences in the clinical efficacy of commonly prescribed 5-HT-active drugs such as selective 5-HT reuptake inhibitors. These data suggest that the treatment of psychiatric disorders such as PTSD may be more effective with the use of 5-HT-targeted drugs in females and AVP-targeted drugs in males.

Oxytocin (OT) and arginine-vasopressin (AVP) act on OT receptors and not AVP V1a receptors to enhance social recognition in adult Syrian hamsters (Mesocricetus auratus)

Social recognition is a fundamental requirement for all forms of social relationships. A majority of studies investigating the neural mechanisms underlying social recognition in rodents have investigated relatively neutral social stimuli such as juveniles or ovariectomized females over short time intervals (e.g., 2h). The present study developed a new testing model to study social recognition among adult males using a potent social stimulus. Flank gland odors are used extensively in social communication in Syrian hamsters and convey important information such as dominance status. We found that the recognition of flank gland odors after a 3min exposure lasted for at least 24h, substantially longer than the recognition of other social cues in rats and mice. Intracerebroventricular injections of OT and AVP prolonged the recognition of flank gland odor for up to 48h. Selective OTR but not V1aR agonists, mimicked these enhancing effects of OT and AVP. Similarly, selective OTR but not V1aR antagonists blocked recognition of the odors after 20min. In contrast, the recognition of non-social stimuli was not blocked by either the OTR or the V1aR antagonists. Our findings suggest both OT and AVP enhance social recognition via acting on OTRs and not V1aRs and that the recognition enhancing effects of OT and AVP are limited to social stimuli.

Brain Formaldehyde is Related to Water Intake behavior.

A promising strategy for the prevention of Alzheimer’s disease (AD) is the identification of age-related changes that place the brain at risk for the disease. Additionally, AD is associated with chronic dehydration, and one of the significant changes that are known to result in metabolic dysfunction is an increase in the endogenous formaldehyde (FA) level. Here, we demonstrate that the levels of uric formaldehyde in AD patients were markedly increased compared with normal controls. The brain formaldehyde levels of wild-type C57 BL/6 mice increased with age, and these increases were followed by decreases in their drinking frequency and water intake. The serum arginine vasopressin (AVP) concentrations were also maintained at a high level in the 10-month-old mice. An intravenous injection of AVP into the tail induced decreases in the drinking frequency and water intake in the mice, and these decreases were associated with increases in brain formaldehyde levels. An ELISA assay revealed that the AVP injection increased both the protein level and the enzymatic activity of semicarbazide-sensitive amine oxidase (SSAO), which is an enzyme that produces formaldehyde. In contrast, the intraperitoneal injection of formaldehyde increased the serum AVP level by increasing the angiotensin II (ANG II) level, and this change was associated with a marked decrease in water intake behavior. These data suggest that the interaction between formaldehyde and AVP affects the water intake behaviors of mice. Furthermore, the highest concentration of formaldehyde in vivo was observed in the morning. Regular water intake is conducive to eliminating endogenous formaldehyde from the human body, particularly when water is consumed in the morning. Establishing good water intake habits not only effectively eliminates excess formaldehyde and other metabolic products but is also expected to yield valuable approaches to reducing the risk of AD prior to the onset of the disease.

Oxytocin induces social communication by activating arginine-vasopressin V1a receptors and not oxytocin receptors.

Arginine-vasopressin (AVP) and oxytocin (OT) and their receptors are very similar in structure. As a result, at least some of the effects of these peptides may be the result of crosstalk between their canonical receptors. The present study investigated this hypothesis by determining whether the induction of flank marking, a form of social communication in Syrian hamsters, by OT is mediated by the OT receptor or the AVP V1a receptor. Intracerebroventricular (ICV) injections of OT or AVP induced flank marking in a dose-dependent manner although the effects of AVP were approximately 100 times greater than those of OT. Injections of highly selective V1a receptor agonists but not OT receptor agonists induced flank marking, and V1a receptor antagonists but not OT receptor antagonists significantly inhibited the ability of OT to induce flank marking. Lastly, injection of alpha-melanocyte-stimulating hormone (α-MSH), a peptide that stimulates OT but not AVP release, significantly increased odor-induced flank marking, and these effects were blocked by a V1a receptor antagonist. These data demonstrate that OT induces flank marking by activating AVP V1a and not OT receptors, suggesting that the V1a receptor should be considered to be an OT receptor as well as an AVP receptor.

Effects of arginine vasopressin on auditory brainstem response and cochlear morphology in rats

This study was conducted to evaluate the relationship between hearing and cochlear histopathology after arginine vasopressin administration in rats. A total of 30 Wistar rats were injected with either 0.02 unit/g of arginine vasopressin or the same amount of isotonic saline solution. The initial auditory brain stem response threshold was recorded and additional measurements were made at 10, 30, 60, and 90 min after injection of arginine vasopressin or isotonic saline solution. The threshold for each timepoint was compared with the initial threshold. Histological quantitative assessment of endolymphatic hydrops in the cochlea was performed using light microscopy and assessment of the basal, intermediate, and marginal cells of the stria vascularis was performed with electron microscopy. The auditory brain stem threshold 60 min after arginine vasopressin injection increased significantly in comparison with the initial threshold (P<0.05). Although the index for endolymphatic hydrops in rats administered arginine vasopressin was not different from that in controls (P>0.05), vacuoles in the intermediate cells were increased significantly in the treated rats (P<0.01). Hearing impairment was detected without endolymphatic hydrops in rats administered arginine vasopressin. An increase of vacuoles in the intermediate cells may account for the hearing impairment induced by arginine vasopressin injection.

Actions of intravenous injections of AVP and oxytocin on plasma ACTH, GH, insulin and glucagon concentrations in goats

This study was conducted to investigate the arginine-vasopressin (AVP)- and oxytocin-induced changes in plasma adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin and glucagon levels and their metabolite concentrations in goats. In this study, five goats were intravenously injected with either AVP (0.3 nmol/kg body weight (BW)) or oxytocin (0.7 IU/kg BW). AVP injection significantly increased ACTH and GH secretions compared to controls, although insulin and glucagon concentrations were not altered. The incremental areas (ICAs) of the ACTH and GH concentrations were higher in the AVP group than in the saline group. Oxytocin injections increased insulin and glucagon secretions, while ACTH level was not altered. GH levels became elevated 30 min after the oxytocin injection. The ICAs of insulin and glucagon after oxytocin was injected were higher than those of the control. Results indicate that AVP is a potent stimulant of ACTH and GH secretions, while oxytocin uses different pathways to regulate insulin and glucagon secretions in goats.

Arginine vasopressin remolds the spontaneous discharges disturbed by amyloid β protein in hippocampal CA1 region of rats

Beta-amyloid peptide (Aβ) aggregated in the brain is the main pathological characteristic of Alzheimer's disease (AD), and a significant decrease in the concentration of arginine vasopressin (AVP) in the brain of AD patients has been reported. Our recent study shows that intracerebroventricular (i.c.v.) injection of AVP protects against Aβ-induced impairments of spatial learning and memory. However, it is still unclear whether the Aβ-induced cognitive deficit is involved in the alteration of central neuronal discharges, and further whether AVP can modulate the electrophysiological change induced by Aβ. The present study thus observed the effects of AVP, Aβ and AVP plus Aβ on the spontaneous discharges of hippocampal CA1 neurons in rats by using multi-channel extracellular recording technique. The results showed that: (1) the average frequency of spontaneous discharges was decreased by i.c.v. injection of 25nmol Aβ25–35; (2) 10nmol AVP induced an increase in spike discharge in the hippocampal CA1 neurons; (3) pretreatment with 10nmol AVP effectively reversed Aβ25–35 induced suppression of spontaneous discharges in hippocampal CA1 region. These in vivo electrophysiological results indicate that AVP, as a hormone and neurotransmitter, can remold the spontaneous discharges disturbed by Aβ and counteract the deleterious effect of Aβ25–35 on neural circuit, suggesting that the activation of central vasopressinergic system may play a beneficial role for the prevention and treatment of cognitive impairments in AD.

Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β

The present study demonstrates a key role for the oxysterol receptor liver X receptor β (LXRβ) in the etiology of diabetes insipidus (DI). Given free access to water, LXRβ(-/-) but not LXRα(-/-) mice exhibited polyuria (abnormal daily excretion of highly diluted urine) and polydipsia (increased water intake), both features of diabetes insipidus. LXRβ(-/-) mice responded to 24-h dehydration with a decreased urine volume and increased urine osmolality. To determine whether the DI was of central or nephrogenic origin, we examined the responsiveness of the kidney to arginine vasopressin (AVP). An i.p. injection of AVP to LXRβ(-/-) mice revealed a partial kidney response: There was no effect on urine volume, but there was a significant increase of urine osmolality, suggesting that DI may be caused by a defect in central production of AVP. In the brain of WT mice LXRβ was expressed in the nuclei of magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. In LXRβ(-/-) mice the expression of AVP was markedly decreased in the magnocellular neurons as well as in urine collected over a 24-h period. The persistent high urine volume after AVP administration was traced to a reduction in aquaporin-1 expression in the kidney of LXRβ(-/-) mice. The LXR agonist (GW3965) in WT mice elicited an increase in urine osmolality, suggesting that LXRβ is a key receptor in controlling water balance with targets in both the brain and kidney, and it could be a therapeutic target in disorders of water balance.