AVP Levels Research Articles

Severe hyperosmolarity and hypernatremia in an adipsic young woman

Combined deficits in arginine vasopressin secretion (AVP) and thirst sensation can result in life threatening hyperosmolality and hypernatremia. Complications include seizures, profound volume contraction and renal failure. Fortunately, this is an uncommon clinical condition, with approximately 70 cases reported in the literature over the past 47 years [1]. Defects in AVP secretion and/or synthesis produce central diabetes insipidus (DI), polyuria with polydipsia, hypernatremia and hyperosmolality. Most awake and alert patients with an intact thirst stimulus will "drink" themselves back to a normal serum sodium and osmolality. However, if there is concomitant destruction of the osmoreceptors that regulate thirst, osmolal and volume homeostasis cannot be maintained. The relationships between urine osmolarity and serum osmolarity and plasma vasopressin levels are vital for distinguishing a reset osmostat from central DI. After obtaining approval from our institutional review board, we retrospectively reviewed the medical record of a 37-year-old patient who presented to our institution with a serum sodium of 176 mEq/l. Admission laboratory examination revealed: hemoglobin 12.8 g/dl; white blood cell count 4.7 × 103/µl, with a normal differential; random serum glucose 91 mg/dl ; sodium 176 mEq/l; plasma osmolality 366 mOsm/kg; BUN 33 mg/dl; serum creatinine 1 mg/dl; calcium 9.5 mg/dl; urine specific gravity 1.032; and urine osmolality 1,172 mOsm/kg. An MRI with contrast of the sella/ pituitary revealed an enhancing mass centered within the suprasellar cistern and anterior third ventricle, measuring 3.0 × 3.9 × 3.4 cm. The lesion appeared to involve the hypothalamus and displaced the optic chiasm inferiorly. Evaluation of pituitary function revealed normal serum levels of thyroid stimulating hormone, AM cortisol, luteinizing hormone, follicle stimulating hormone and prolactin. Figure 1 illustrates the relationship between measured serum AVP levels and serum osmolality. Figure 2 shows the relationship between measured urine and serum osmolality. If the serum AVP levels were not available, it would appear as though the patient had a reset osmostat. The kidneys appear to appropriately generate maximally concentrated urine at a serum osmolality above 348 but are unable to below this value. When compared with the normal curve, our patient's AVP levels were lower than expected for the corresponding osmolality. This pattern is consistent with a partial central DI. She does not have a reset osmostat. In the presence of significant volume contraction and a reduced GFR, her kidneys produced more concentrated urine despite markedly decreased central vasopressin production. As the volume contraction abated and the GFR improved, polyuria recurred, despite persistent hyperosmolarity and hypernatremia.

Urine-concentrating defects exacerbate with age in male offspring with a low-nephron endowment

Fetal uninephrectomy (uni-x) in male sheep at 100 days of gestation (term = 150 days) reduces overall nephron endowment without affecting birth weight. Offspring have a lower glomerular filtration rate (GFR) and elevated mean arterial pressure (MAP) at 6 mo of age. This study investigated whether this reduction in renal function was associated with impaired urine-concentrating ability at 6 mo of age and exacerbated with ageing (4 yr) and examined response to 1) nonpressor dose of exogenous arginine vasopressin (AVP; 0.2 μg·kg(-1)·h(-1) iv) and 2) 30 h of water deprivation. Basal MAP was higher in uni-x animals at both ages, and became further elevated with age compared with the sham group (elevation in MAP with age; sham: ~4 mmHg, uni-x: 9 mmHg, P(group × age) < 0.01). GFR declined with ageing in both groups with the decrease being greater with age in the uni-x group (further 26%, P(group × age) < 0.001). In response to AVP infusion, urine osmolality increased in both treatment groups; this response was significantly lower in the uni-x animals and became further reduced with ageing. Uni-x animals had reduced renal expression of vasopressin-2 receptor and aquaporin-2 at both ages (P < 0.01). The increase in plasma AVP levels in response to dehydration was similar between the treatment groups, suggesting the urine-concentrating defect was associated with these renal gene changes rather than defects in AVP secretion. Renal insufficiency due to a low-nephron endowment increases the risk of hypertension and chronic renal disease and may incur greater vulnerability to physiological challenges such as water deprivation as observed in the uni-x animals.

Augmented central nitric oxide production inhibits vasopressin release during hemorrhage in acute alcohol-intoxicated rodents

Acute alcohol intoxication (AAI) attenuates the AVP response to hemorrhage, contributing to impaired hemodynamic counter-regulation. This can be restored by central cholinergic stimulation, implicating disrupted signaling regulating AVP release. AVP is released in response to hemorrhage and hyperosmolality. Studies have demonstrated nitric oxide (NO) to play an inhibitory role on AVP release. AAI has been shown to increase NO content in the paraventricular nucleus. We hypothesized that the attenuated AVP response to hemorrhage during AAI is the result of increased central NO inhibition. In addition, we predicted that the increased NO tone during AAI would impair the AVP response to hyperosmolality. Conscious male Sprague-Dawley rats (300-325 g) received a 15-h intragastric infusion of alcohol (2.5 g/kg + 300 mg·kg(-1)·h(-1)) or dextrose prior to a 60-min fixed-pressure hemorrhage (∼40 mmHg) or 5% hypertonic saline infusion (0.05 ml·kg(-1)·min(-1)). AAI attenuated the AVP response to hemorrhage, which was associated with increased paraventricular NO content. In contrast, AAI did not impair the AVP response to hyperosmolality. This was accompanied by decreased paraventricular NO content. To confirm the role of NO in the alcohol-induced inhibition of AVP release during hemorrhage, the nitric oxide synthase inhibitor, nitro-l-arginine methyl ester (l-NAME; 250 μg/5 μl), was administered centrally prior to hemorrhage. l-NAME did not further increase AVP levels during hemorrhage in dextrose-treated animals; however, it restored the AVP response during AAI. These results indicate that AAI impairs the AVP response to hemorrhage, while not affecting the response to hyperosmolality. Furthermore, these data demonstrate that the attenuated AVP response to hemorrhage is the result of augmented central NO inhibition.

Neonatal endotoxin exposure changes neuroendocrine, cardiovascular function and mortality during polymicrobial sepsis in adult rats

Our aim was to investigate whether neonatal LPS challenge may improve hormonal, cardiovascular response and mortality, this being a beneficial adaptation when adult rats are submitted to polymicrobial sepsis by cecal ligation and puncture (CLP). Fourteen days after birth, pups received an intraperitoneal injection of lipopolysaccharide (LPS; 100μg/kg) or saline. After 8–12weeks, they were submitted to CLP, decapitated 4, 6 or 24h after surgery and blood was collected for vasopressin (AVP), corticosterone and nitrate measurement, while AVP contents were measured in neurohypophysis, supra-optic (SON) and paraventricular (PVN) nuclei. Moreover, rats had their mean arterial pressure (MAP) and heart rate (HR) evaluated, and mortality and bacteremia were determined at 24h. Septic animals with neonatal LPS exposure had higher plasma AVP and corticosterone levels, and higher c-Fos expression in SON and PVN at 24h after surgery when compared to saline treated rats. The LPS pretreated group showed increased AVP content in SON and PVN at 6h, while we did not observe any change in neurohypophyseal AVP content. The nitrate levels were significantly reduced in plasma at 6 and 24h after surgery, and in both hypothalamic nuclei only at 6h. Septic animals with neonatal LPS exposure showed increase in MAP during the initial phase of sepsis, but HR was not different from the neonatal saline group. Furthermore, neonatally LPS exposed rats showed a significant decrease in mortality rate as well as in bacteremia. These data suggest that neonatal LPS challenge is able to promote beneficial effects on neuroendocrine and cardiovascular responses to polymicrobial sepsis in adulthood.

Brain Gαz/Gαq subunit protein‐gated pathways participate in regulating AVP secretion and urine output during conditions in which water homeostasis is challenged

Hypothesis Brain Gαz/Gαq protein pathways play a critical role in maintaining water homeostasis by regulating AVP release and urine output in vivo. Methods Sprague-Dawley rats were pre-treated intracerebroventricularly (i.c.v.) with an oligodeoxynucleotide (ODN) targeted towards a Gαz, Gαq, or a scrambled (SCR) sequence (24hrs, 25 μg; N=6/group). In volume overload studies, urine output (V) was measured for 90-min in instrumented rats subjected to an acute i.v. isotonic saline volume expansion (VE, 3%BW for 30-min). In volume deprivation (VD) studies, spontaneous urine output was measured before (control) and during water restriction for 6-hr, after which rats were sacrificed for trunk blood collection and plasma AVP measurement. Urine Output (V) VE Study Control (μl/min) Peak (μl/min) (30-min post-VE) Cumulative (ml) (120 min post-VE) SCR ODN 24.6±2.5 135.2±12.6* 8.67+/− 0.80 Gz ODN 18.1±2.6 76.5±8.7*τ 6.70+/− 0.40τ Gq ODN 26.6±5.2 136.6±10.7* 10.79 +/− 0.70τ VD Study Control (ml/3hr) V: 1–3 hrs Post-VD (ml) V: 3–6 hrs Post-VD (ml) Plasma [AVP] (pg/ml) SCR ODN 2.35±0.63 1.78±0.42 0.78±0.23* 11.3±0.6 Gz ODN 1.76±0.20 1.53±0.28 0.58±0.12* 8.7±0.8τ Gq ODN 2.56±0.41 2.02±0.60 2.59±0.60 5.1±0.5τ * P<0.05 vs. resp. control value; τ p<0.05 vs. group SCR value. Results Selective down-regulation of central Gα protein pathways significantly blunted (Gz ODN) or enhanced (Gq ODN) the diuretic response to acute VE. During water deprivation, down-regulation of brain Gαq proteins prevented the maximal increase in plasma AVP levels and water retention. Conclusions Brain Gαz/Gαq subunit protein-gated pathways play a physiological role in regulating AVP secretion and urine output during conditions in which water homeostasis is challenged. NIH DK4337, HL071212, P20RR018766 and AHA 0855293E to DRK

Pharmacologic Rescue of Impaired Cognitive Flexibility, Social Deficits, Increased Aggression, and Seizure Susceptibility in Oxytocin Receptor Null Mice: A Neurobehavioral Model of Autism

Oxytocin (OT) has been suggested as a treatment to improve social behavior in autistic patients. Accordingly, the OT (Oxt(-/-)) and the OT receptor null mice (Oxtr(-/-)) display autistic-like deficits in social behavior, increased aggression, and reduced ultrasonic vocalization. Oxtr(-/-) mice were characterized for general health, sociability, social novelty, cognitive flexibility, aggression, and seizure susceptibility. Because vasopressin (AVP) and OT cooperate in controlling social behavior, learning, and aggression, they were tested for possible rescue of the impaired behaviors. Primary hyppocampal cultures from Oxtr(+/+) and Oxtr(-/-) mouse embryos were established to investigate the balance between gamma-aminobutyric acid (GABA) and glutamate synapses and the expression levels of OT and AVP (V1a) receptors were determined by autoradiography. Oxtr(-/-) mice display two additional, highly relevant, phenotypic characteristics: 1) a resistance to change in a learned pattern of behavior, comparable to restricted interests and repetitive behavior in autism, and 2) an increased susceptibility to seizures, a frequent and clinically relevant symptom of autism. We also show that intracerebral administration of both OT and AVP lowers aggression and fully reverts social and learning defects by acting on V1a receptors and that seizure susceptibility is antagonized by peripherally administered OT. Finally, we detect a decreased ratio of GABA-ergic versus total presynapses in hippocampal neurons of Oxtr(-/-) mice. Autistic-like symptoms are rescued on administration of AVP and OT to young Oxtr(-/-) adult animals. The Oxtr(-/-) mouse is thus instrumental to investigate the neurochemical and synaptic abnormalities underlying autistic-like disturbances and to test new strategies of pharmacologic intervention.

Prenatal presentation of transient central diabetes insipidus

Nephrogenic diabetes insipidus (DI) in the foetus has been described as a rare presentation of severe polyhydramnios. We report a case of foetal central DI, characterised by severe polyhydramnios. Significant polyuria was noted at birth. Serum AVP level was un-measurable (<0.5 pg/ml). A dramatic response to intravenous dDAVP (desmopressin) was noted confirming central DI. Further investigations did not reveal a recognised cause for central or nephrogenic DI. The infant thrived well on a small dose of oral desmopressin until the age of 12 months. At 13 months, a water deprivation test revealed a normal ability to concentrate urine without desmopressin, and subsequently, the infant has thrived without further treatment. The transient nature of the central DI remains obscure but could be explained by a maturational delay in the tissues involved in AVP synthesis or release, during intrauterine life and infancy. Both nephrogenic and central DI should be considered as a cause of severe polyhydramnios. This may help to guide prompt intensive management and investigation, with attention to vascular access, central venous pressure, urine output monitoring and replacement.

Prolactin promotes oxytocin and vasopressin release by activating neuronal nitric oxide synthase in the supraoptic and paraventricular nuclei

Prolactin (PRL) stimulates the secretion of oxytocin (OXT) and arginine AVP as part of the maternal adaptations facilitating parturition and lactation. Both neurohormones are under the regulation of nitric oxide. Here, we investigate whether the activation of neuronal nitric oxide synthase (nNOS) in the hypothalamo-neurohypophyseal system mediates the effect of PRL on OXT and AVP release and whether these effects operate in males. Plasma levels of OXT and AVP were measured in male rats after the intracerebroventricular injection of PRL or after inducing hyperprolactinemia by placing two anterior pituitary glands under the kidney capsule. NOS activity was evaluated in the paraventricular (PVN) and supraoptic (SON) hypothalamic nuclei by NADPH-diaphorase histochemistry and in hypothalamic extracts by the phosphorylation/inactivation of nNOS at Ser(847). Elevated central and systemic PRL correlated with increased NOS activity in the PVN and SON and with higher OXT and AVP circulating levels. Notably, treatment with 7-nitroindazole, a selective inhibitor of nNOS, prevented PRL-induced stimulation of the release of both neurohormones. Also, phosphorylation of nNOS was reduced in hyperprolactinemic rats, and treatment with bromocriptine, an inhibitor of anterior pituitary PRL secretion, suppressed this effect. These findings suggest that PRL enhances nNOS activity in the PVN and SON, thereby contributing to the regulation of OXT and AVP release. This mechanism likely contributes to the regulation of processes beyond those of female reproduction.

The stress hormone copeptin: a new prognostic biomarker in acute illness

Stress is defined as anything that throws the body out of homeostatic balance; for example an acute illness. Any stressor which activates the hypothalamo-pituitary-adrenal (HPA) axis leads to an increase in concentrations of the adrenal stress hormone, cortisol. One of the major hypothalamic stress hormones, which is stimulated by different stressors, is vasopressin (AVP). However, measurement of circulating AVP levels is challenging because it is released in a pulsatile pattern, it is unstable and is rapidly cleared from plasma. AVP derives from a larger precursor peptide (pre-provasopressin) along with copeptin which is released in an equimolar ratio to AVP and is more stable in the circulation and easy to determine. Copeptin levels were found to closely mirror the production of AVP. We have shown that copeptin more subtly mirrors the individual stress level compared to cortisol. Due to the positive association of copeptin with the severity of illness and outcome, copeptin has been proposed as a prognostic marker in acute illness. The prognostic accuracy of copeptin has been analysed in sepsis, pneumonia, lower respiratory tract infections, stroke and other acute illnesses. Thereby, copeptin was found to accurately mirror disease severity and to discriminate patients with unfavourable outcomes from patients with favourable outcomes. Copeptin improves the prognostic information provided by commonly used clinical scoring instruments. Importantly, interpretation of copeptin levels must always consider the clinical setting. An accurate prognostic assessment has the potential to guide interventions and effectively plan and monitor rehabilitation and, thus optimise the management of individual patients and the allocation of limited health care resources. Future intervention studies must prove the value of copeptin in clinical decision making and in improving the overall medical management of patients with acute illnesses.

Interleukin-18 deficiency reduces neuropeptide gene expressions in the mouse amygdala related with behavioral change

In this study, we examined the effects of IL-18 deficiency on behaviors and gene expression profiles in 6 brain regions. IL-18 −/− mice reduced depressive-like behavior and changed gene expressions predominantly in the amygdala compared with wild-type mice. Pathway analysis of the differentially expressed genes ranked behavior as the top-scored biological function. Of note, the absence of IL-18 decreased Avp, Hcrt, Oxt, and Pmch mRNA levels and the number of arginine vasopressin- and oxytocin-positive cells in the amygdala, but not in the hypothalamus. Our results suggest that IL-18-dependent vasopressinergic and oxytocinergic circuitry in the amygdala may regulate depressive-like behaviors in mice.

Immunoregulation by the neurohypophysis

The role of the neurohypophysial hormones on immunoregulation has not been completely elucidated. To obtain a deeper insight, groups of Lewis rats were subjected to sham operation (SHAM), anterior (AL) or neurointermediate pituitary lobectomy (NIL) or total hypophysectomy (HYPX) and immunized for adjuvant induced arthritis (AIA) or experimental autoimmune encephalomyelitis (EAE). Intact control groups were included for reference. Groups were sacrificed 15 days postimmunization. Serum levels of PRL, ACTH and AVP, and spleenic ILs mRNA expression and macrophages number were assessed. In the AIA experiment, SHAM animals showed normal PRL, ACTH and AVP serum levels, increased expression of ILs 1 and 12, no changes in the remaining ILs, and significant increase in macrophages number. In the AL rats, normal AVP and low PRL and ACTH serum levels occurred. Except TNFα, ILs‐1,‐2,‐6,‐10,‐12, INFγ and macrophages number were significantly increased. In NIL rats, low AVP and normal PRL and ACTH levels occurred, and no alterations in ILs expression and macrophages number were found. In HYPX animals, low PRL, ACTH and AVP were apparent, while ILs‐1 and ‐12 and macrophages number were significantly increased. In general, similar results were obtained in EAE groups. The results indicate that immune responses can occur in absence of the pituitary gland and that AVP is an important immunoregulator.Supported by UAA and CONACYT. México

Nesfatin‐1 Stimulates Stress Hormone Secretion

Cellular actions of nesfatin‐1 on oxytocin (OT), vasopressin (AVP) and corticotropin releasing factor (CRF) neurons (J Neuroendocrinol 20:255,2008), the activation of early gene expression in those types of neurons following stress (Brain Res 1300:114,2009), and the ability of nesfatin‐1 to elicit fear and anxiety behaviors (Psychopharmacol 201:115,2008; AJP 297:R330,2009) suggested a role for nesfatin‐1 in the stress response. In conscious, unrestrained male rats i.c.v. administration of 180 pmole nesfatin‐1 resulted in significant increases in plasma levels of AVP (vehicle: 1.9±0.5, n=8; nesfatin‐1: 10.0±3.4 pg AVP/ml, n=8, p = 0.018) and ACTH (vehicle: 6.0±1.4; nesfatin‐1: 28.5±7.7 pg ACTH/ml; p&lt;0.01) 10 minutes later. Plasma OT levels were unchanged. The actions of nesfatin‐1 on food intake and cardiovascular function are dependent upon activation of POMC neurons (AJP 297:R330,2009) and roles for OT in those actions have been reported. We suggest that nesfatin‐1 activates stress hormone secretion by releasing AVP and CRF but that the ability of nesfatin‐1 to activate OT neurons reflects an action to release OT centrally and not into the peripheral plasma.

Peripheral vs central administration of NaCl differently modulates vasopressin secretion through the regulation of PVN Gαq sub‐unit proteins

HypothesisPVN Gαq sub‐unit protein gated pathways, which are stimulatory on AVP secretion, are endogenously down‐regulated to prevent excess AVP secretion following peripheral, but not central, administration of NaCl.MethodsSprague‐Dawley rats were maintained on 0.4% or 8% NaCl chow, or were infused intracerebroventricularly (i.c.v.) with aCSF or 0.8M NaCl aCSF for 21‐days (N=5/gp). PVN tissue was examined for Gαz &amp; Gαq protein expression (normalized to GAPDH) via immunoblotting. Plasma AVP levels were determined via ELISA. In rats treated chronically as described above, N/OFQ (peptide inhibitor of AVP) was injected i.c.v. (5.5 nmol) and urine output was collected for 90‐min (10‐min periods). Separate rats infused with 0.8M NaCl (21‐days) were pre‐treated i.c.v. with a Gαq oligodeoxynucleotide (ODN; 25 μg) 24‐h prior to plasma AVP and PVN Gαz/q protein measurement.Results 0.4% NaCl diet 8% NaCl diet aCSF i.c.v. infusion 0.8M NaCl aCSF i.c.v. infusion 0.8M NaCl aCSF i.c.v. infusion + Gαq ODN PVN Gαq Protein levels [ODU] 0.99±0.07 0.12±0.05* 1.16±0.06 1.09±0.08 0.22±0.04# PVN Gαz Protein levels [ODU] 2.24±0.13 2.34±0.12 2.01±0.12 2.12±0.13 2.08±0.11 AVP [pg/ml] 1.39±0.07 1.38±0.14 1.50±0.17 2.12±0.17# 0.99±0.06# Peak Diuresis to N/OFQ [μl/min] 199±16 191±11 177±23 54±12# T.B.D. *, # Sig diff vs 0.4% NaCl or aCSF gp;ConclusionIn response to a peripheral salt load, which does not elevate CSF NaCl levels, the down‐regulation of PVN Gαq proteins is an endogenous counter regulatory mechanism to prevent salt‐induced increases in plasma AVP levels and water retention. When CSF NaCl is increased, this counter‐regulatory mechanism fails, leading to increased circulating AVP and an impaired diuretic ability. AHA 2250585, DK43337, HL071212, AHA 0855293E, P20 RR018766

The blockade of oxytocinergic receptors in the CeA modify VP plasma levels and mRNA expression induced by hypertonic BVE in the rat.

We investigated the effects of oxytocin (OT) and the oxytocinergic antagonist vasotocin (OVT) injection in the central amygdala (CeA) in the regulation of vasopressin (VP) mRNA expression in the hypothalamus and VP plasma levels in response to hypertonic blood volume expansion (hyper BVE). Male Wistar rats with cannulas unilaterally in the CeA were subjected to BVE (2 ml/100 g bw) over 1 minute. OT, OVT or vehicle was injected into the CeA 20 min before the BVE. Five min after BVE rats were decapitated and the blood was collected for VP plasma determination. Another group was perfused 40 min after BVE. Brain sections of the paraventricular (Pa) and the supraoptic (SON) nuclei were collected for in situ hybridization using a 35S‐labeled VP probe. OT injection in the CeA increased plasma VP levels after hyper BVE and reduced VP mRNA in the PaLM. OVT reduced plasma AVP levels following a reduction VP mRNA in the PaLM and SON. Our data suggest that OT in the CeA may modulate the physiological mechanisms involved in plasma AVP release but the time course of the hormonal release has been shown dissociated from the genomic AVP expression in the PaLM. We hypothesize that the blockade of OT CeA receptors with OVT may activate an inhibitory input to vasopressinergic magnocellular neurons in the hypothalamus leading to the decrease in plasma AVP levels that can be strongly correlated with the reduction in the genomic AVP mRNA.

CB 1 modulation of hormone secretion, neuronal activation and mRNA expression following extracellular volume expansion

The endocannabinoid system includes important signaling molecules that are involved in several homeostatic and neuroendocrine functions. In the present study, we evaluated the effects of the type 1 cannabinoid (CB 1) receptor antagonist, rimonabant (10 mg/kg, p.o.), on hormone secretion, neuronal activation and mRNA expression in the hypothalamus following isotonic (I-) or hypertonic (H-) extracellular volume expansion (EVE). The total nitrate content in the PVN and SON was also assessed under the same experimental conditions. Our results showed that OT and AVP plasma concentrations were increased in response to H-EVE, while decreased AVP levels were found following I-EVE. Accordingly, both I- and H-EVE stimulated oxytocinergic neuronal activation, as evidenced by the increased number of c-Fos/OT double labeled neurons in the hypothalamus. The vasopressinergic cells of the PVN and SON, however, were only activated in response to H-EVE. Furthermore, increased amounts of both AVP and OT mRNAs were found in the hypothalamus following EVE. Pretreatment with rimonabant significantly potentiated hormone secretion and also vasopressinergic and oxytocinergic neuronal activation induced by EVE, although decreased AVP and OT mRNA expression was found in the hypothalami of rimonabant pretreated groups. In addition, the nitrate content in the PVN and SON was not altered in response to EVE or rimonabant pretreatment. Taken together, these results suggest that the CB 1 receptor may modulate several events that contribute to the development of appropriate responses to increased fluid volume and osmolality.

Influences of hypertonic and hypovolemic treatments on vasopressin response in propylthiouracil (PTU) induced hypothyroid rat and effect on supplementation with L-thyroxine

This study was performed to investigate the effects of L-thyroxine treatment on plasma vasopressin (AVP) levels in rats with hypothyroidism induced by propylthiouracil (PTU). Animals were separated into three groups each having 6 rats: control, PTU, PTU+L-thyroxine groups. Then, the groups were further divided into 3 sub-groups including 6 rats (a; basal, b; hypertonic stimulated and c; hypovolemic stimulated). At the end of the experiments all rats were decapitated in order to obtain plasma samples for analysis in terms of Hct, osmolality, TT 3 , TT 4 and vasopressin. Haematocrit (Hct) levels were the highest in hypovolemic stimulated sub-group (P < 0.001). Osmolality levels were higher in hypertonic stimulated sub-groups (P < 0.001). Total T 3 and T 4 values were the lowest in the PTU group and the highest in the L-thyroxine treated group (P < 0.001). Plasma AVP levels were reduced by hypothyroidism. However, L-thyroxine treatment after the hypothyroidism prevented this reduction (P < 0.001). Vasopressin responses to basal, hypovolemic and hypertonic stimulations were the lowest in the PTU group (P < 0.001). The results of the present study show that basal and stimulated plasma vasopressin levels are reduced in PTU-induced hypothyroidism. However, L-thyroxine treatment following hypothyroidism prevents this reduction.

Hypothyroidism: Clinical Features

Hypothyroidism: Clinical Features

Effect of serotonergic system on AVP secretion induced by physical exercise

The present study was undertaken in order to establish the possible involvement of serotonergic receptors in the control of physical exercise-stimulated vasopressin secretion. Twenty-one healthy men (divided in three groups of seven) underwent bicycle-ergometer tests until exhaustion: exercise control test (n=21), exercise plus ondansetron, selective 5-HT3 antagonist (n=7), exercise plus buspirone, selective 5-HT1A receptor agonist (n=7), exercise plus sumatriptan, selective 5-HT1D receptor agonist (n=7). AVP levels, physiological and biochemical variables were measured and compared during tests. Results showed that exercise-induced AVP rise did not change after the administration of buspirone and sumatriptan. In contrast, the administration of ondansetron significantly reduced physical exercise-induced AVP rise. Mean peak levels during physical exercise were 4.9 times higher than basal values in the control test and 2.6 times higher than basal values in the ondansetron plus exercise test. These data demonstrate that 5-HT3 serotonergic receptors at least partially mediate the AVP response to physical exercise. On the other hand, 5-HT1A and 5-HT1D serotonergic receptors do not appear to be involved in the control of AVP secretion during exercise.

Copeptin – diagnostischer Parameter, Biomarker, beides?

Copeptin denominates the C-terminal fragment of the vasopressin (AVP) precursor hormone. Circulating copeptin levels reflect the activity of the AVP system and correlate closely with plasma osmolality. The measurement of stimulated plasma AVP levels is crucial in the differential diagnosis of diabetes insipidus, particularly the characterization of partial forms, and is used to diagnose primary polydipsia. However, determination of AVP levels is technically demanding, and validated assays are not readily available for clinical routine. Recently, a reliable sandwich immunoassay for measurement of serum or plasma copeptin levels has been introduced. Assaying stimulated copeptin levels will be helpful in the differential diagnosis of diabetes insipidus. Recent studies suggest that measurement of copeptin, once the assay is commercially available, might prove useful in the workup of hyponatremic disorders. Moreover, copeptin has been found to be a prognostically relevant biomarker in a variety of illnesses such as sepsis, shock, pneumonia, acute exacerbation of COPD, heart failure, and myocardial infarction.

TRANSIENT CENTRAL CHOLINERGIC ACTIVATION ENHANCES SYMPATHETIC NERVOUS SYSTEM ACTIVITY BUT DOES NOT IMPROVE HEMORRHAGE-INDUCED HYPOTENSION IN ALCOHOL-INTOXICATED RODENTS

Morbidity and mortality after traumatic injury and hemorrhagic shock (HS) are exacerbated in the alcohol-intoxicated individual. The level of hypotension at the time of admittance into the emergency department is a critical indicator of outcome from injury. Previously, we have demonstrated that acute alcohol intoxication (AAI) decreases basal mean arterial blood pressure (MABP), exaggerates hypotension throughout HS, and attenuates the pressor response to fluid resuscitation in male rodents. This AAI-induced impaired hemodynamic counter-regulation to blood loss is associated with dampened neuroendocrine activation (i.e., epinephrine, norepinephrine, and arginine vasopressin [AVP] release). We hypothesize that the blunted neuroendocrine response is the principal mechanism involved in hemodynamic instability during and after HS in AAI. The present study investigates whether enhancing central cholinergic activity via intracerebroventricular (ICV) choline, a precursor of acetylcholine, would restore the neuroendocrine response and, as a result, improve hemodynamic compensation after HS. Chronically catheterized, conscious, male Sprague-Dawley rats (225-250 g) received a primed 15-h alcohol infusion (30% wt/vol; total approximately 8 g x kg(-1)) before ICV choline (150 microg) injection and were subsequently subjected to fixed-volume HS (50%) and fluid resuscitation with lactated Ringer's solution (2x volume removed). There were a total of eight experimental groups (n = 5-12 rats per group): alcohol-treated not hemorrhaged (alcohol/sham), dextrose-treated not hemorrhaged (dextrose/sham), alcohol-treated hemorrhaged (alcohol/hemorrhage), and dextrose-treated hemorrhaged (dextrose/hemorrhage), with ICV choline or water injection. Intracerebroventricular choline immediately increased basal MABP in both control (16%) and AAI animals (12%), but did not alter MABP after HS in either group. Intracerebroventricular choline increased basal plasma epinephrine (196%), norepinephrine (96%), and AVP (145%) and enhanced the HS-induced increase in epinephrine and AVP, without altering norepinephrine responses to HS, in control animals. Acute alcohol intoxication blunted choline-induced neuroendocrine activation and prevented the HS-induced increase in norepinephrine, without affecting post-HS epinephrine and AVP levels. Intracerebroventricular choline administration to AAI animals enhanced the HS-induced increase in epinephrine without affecting post-HS norepinephrine or AVP. These results indicate that ICV choline produced immediate neuroendocrine activation and elevation in MABP that was not sustained sufficiently to improve hemodynamic counter-regulation in alcohol-treated animals.