Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously showed that the cytostatic drug hydroxyurea (HU) activates the hypothalamo-pituitary-adrenal (HPA) axis in intact rats, whereas it is lethal in rats with impaired HPA function. In these animals, HU toxicity is mediated by increased circulating levels of proinflammatory cytokines, whose secretion cannot be counteracted by glucocorticoids, suggesting that HPA activation blunts HU toxicity. Here we investigated the mechanisms through which HU activates the HPA axis, looking at the direct effects of the drug on the isolated hypothalamus. We found that HU significantly increases the release of arginine vasopressin but not that of corticotrophin-releasing hormone in short-term incubation experiments. The levels of arginine vasopressin are also increased in the hypothalamus and systemic circulation 2 h after the in vivo administration of the drug. Furthermore, HU increased significantly the expression of interleukin-6 and, to a lesser extent, interleukin-1beta in the hypothalamus. Interestingly, experiments with HU on primary cultures of rat microglia and astrocytes suggested that the increase in cytokine gene expression observed in hypothalamic explants is not accounted for by glial cells. Since both vasopressin and cytokines can activate the HPA axis, our present findings provide a reasonable explanation of the HPA activation elicited by HU in vivo in the rat.
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PMID:Hydroxyurea induces vasopressin release and cytokine gene expression in the rat hypothalamus. 1684 35

Drinking 2% NaCl decreases interleukin (IL)-1beta in the neural lobe and enhances IL-1 Type 1 receptor expression in magnocellular neurones and pituicytes. To quantify cytokine depletion from the neural lobe during progressive salt loading and determine whether the changes are reversible and correspond with stores of vasopressin (VP) or oxytocin (OT), rats were given water on day 0 and then 2% NaCl to drink for 2, 5, 8 or 5 days followed by 5 days of water (rehydration). Control rats drinking only water were pair-fed amounts eaten by 5-day salt-loaded animals. Animals were decapitated on day 8, the neural lobe frozen and plasma hormones analysed by radioimmunoassay (OT, VP) or enzyme-linked immunosorbent assay (IL-1beta). IL-1beta, VP and OT in homogenates of the neural lobe were quantified by immunocapillary electrophoresis with laser-induced fluorescence detection. Differences were determined by ANOVA, Tukey's t-test, Dunnett's procedure, Fisher's least significant difference and linear regression analysis. In response to salt-loading, rats lost body weight similar to pair-fed controls, drank progressively more 2% NaCl and excreted greater urine volumes. Plasma VP increased at days 2 and 8 of salt-loading, whereas osmolality, OT and cytokine were enhanced after 8 days with IL-1beta remaining elevated after rehydration. In the neural lobe, all three peptides decreased progressively with increasing duration of salt-loading (IL-1beta, r2 = 0.98; OT, r2 = 0.94; VP, r2 = 0.93), beginning on day 2 (IL-1beta; VP) or 5 (OT), with only VP replenished by rehydration. IL-1beta declined more closely (P < 0.0001; ANOVA interaction analysis) with OT (r2 = 0.96) than VP (r2 = 0.86), indicative of corelease from the neural lobe during chronic dehydration. Local effects of IL-1beta on magnocellular terminals, pituicytes and microglia in the neural lobe with activation of forebrain osmoregulatory structures by circulating cytokine may sustain neurosecretion of OT and VP during prolonged salt-loading.
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PMID:Response of interleukin-1beta in the magnocellular system to salt-loading. 1707 68

Systolic heart failure (HF) is a progressive disorder that often begins with asymptomatic left ventricular (LV) systolic dysfunction and culminates in symptoms from fluid overload and poor end-organ perfusion. The progression to symptomatic HF is accompanied by marked activation of neurohormonal and cytokine systems, as well as a series of adaptive LV anatomical and functional changes, collectively referred to as LV remodelling. However, the mechanisms underlying symptom appearance have not been delineated and the weight of experimental and clinical evidence suggests that the development of symptomatic HF occurs independently of the haemodynamic status of the patient. The left atrium is a muscular chamber strategically located between the left ventricle and the pulmonary circulation with important mechanical function (modulation of LV filling), which is closely coupled with its endocrine (atrial natriuretic peptide synthesis and secretion) and regulatory (contribution to the control of sympathetic activity and vasopressin release) functions. In this narrative review we provide evidence supporting the concept that left atrial dilation and systolic dysfunction (left atrial remodelling) contributes to the progression of asymptomatic LV dysfunction to chronic symptomatic systolic HF as it is a prerequisite for the development of the pulmonary congestion and marked neuronhormoral activity that characterize the symptomatic state.
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PMID:Left atrial remodelling contributes to the progression of asymptomatic left ventricular systolic dysfunction to chronic symptomatic heart failure. 1745 Apr 25

Volatile anesthetics such as isoflurane have been shown to offer anti-inflammatory effects during experimental endotoxemia whereas the alpha-adrenergic vasopressor norepinephrine exhibits proinflammatory properties on systemic cytokine release under the same conditions. However, during major surgery and in patients with systemic inflammatory response syndrome or sepsis both agents are frequently administered concurrently. We therefore aimed to investigate the influence of preexisting i.v. administration of noradrenaline or vasopressin on the anti-inflammatory effects of isoflurane during experimental endotoxemia. Anesthetized, ventilated Sprague-Dawley rats (n=7 per group) were randomly treated. In the LPS-only group, animals received lipopolysaccharide (LPS, 5 mg/kg, i.v.) with no further specific treatment. In the LPS-isoflurane group, isoflurane inhalation at 1 MAC was initiated simultaneously with induction of endotoxemia (LPS 5 mg/kg, i.v.). Animals in the LPS-isoflurane-norepinephrine group received norepinephrine infusion at 50 microg/kg/h 10 min prior to injection of LPS and inhalation of isoflurane. In the LPS-isoflurane-vasopressin group, vasopressin was administered at 0.5 IE/kg/h 10 min prior to LPS and isoflurane. In the LPS-norepinephrine and the LPS-vasopressin groups the infusion of each vasopressor was started prior to LPS injection without any application of isoflurane. A Sham group served as the control. After 4 h of endotoxemia, plasma levels of TNFalpha, IL-1beta and IL-10 were measured. Alveolar macrophages (AM) were cultured ex vivo for nitrite assay. Induction of endotoxemia resulted in a significant rise in measured plasma cytokines and nitrite production from cultured AM. Inhalation of isoflurane significantly attenuated plasma levels of TNFalpha (-65%) and IL-1beta (-53%) compared to the LPS-only group whereas it had no effect on nitrite production from cultured AM. Preexisting infusions of norepinephrine or vasopressin abolished the anti-inflammatory effects of isoflurane. The data demonstrate that the administration of norepinephrine or vasopressin both counteracted the anti-inflammatory effects of inhaled isoflurane on proinflammatory cytokine release during experimental endotoxemia in rats.
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PMID:Norepinephrine and vasopressin counteract anti-inflammatory effects of isoflurane in endotoxemic rats. 1778 93

Interleukin (IL)-1beta is present throughout the magnocellular neuroendocrine system and co-depletes with oxytocin and vasopressin from the neural lobe during salt-loading. To examine whether IL-1beta is released from the dendrites/soma of magnocellular neurones during osmotic stimulation, microdialysis adjacent to the supraoptic nucleus (SON) in conscious rats was combined with immunocapillary electrophoresis and laser-induced fluorescence detection to quantify cytokine in 5-min dialysates collected before (0-180 min; basal), and after (180-240 min), hypertonic saline injected s.c. (1.5 m NaCl). Osmotic release of IL-1beta was compared after inhibiting local voltage-gated channels for Na+ (tetrodotoxin) and Ca2+ (cadmium and nickel) or by reducing intracellular Ca2+ stores (thapsigargin). Immunohistochemistry combined with microdialysis was used to localise cytokine sources (IL-1beta+) and microglia (OX-42+). Under conditions of microdialysis, the basal release of IL-1beta+ in the SON area was measurable and stable (pg/ml; mean +/- SEM) from 0-60 min (2.2 +/- 0.06), 60-120 min (2.32 +/- 0.05) and 120-180 min (2.33 +/- 0.06), likely originating locally from activated microglia (OX42+; IL-1beta+; ameboid, hypertrophied) and magnocellular neurones expressing IL-1beta. In response to osmotic stimulation, IL-1beta increased progressively in dialysates of the SON area by a mechanism dependent on intracellular Ca2+ stores sensitive to thapsigargin and, similar to dendritic secretion of oxytocin and vasopressin, required local voltage-gated Na+ and Ca2+ channels for activation by osmoregulatory pathways from the forebrain. During osmotic stimulation, neurally dependent release of IL-1beta in the SON area likely upregulates osmosensitive cation currents on magnocellular neurones (observed in vitro by others), to facilitate dendritic release of neurohypophysial hormones.
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PMID:Interleukin-1beta release in the supraoptic nucleus area during osmotic stimulation requires neural function. 1875 52

During the brain's innate immune response microglia, astroglia and ependymal cells resolve/repair damaged tissue and control infection. Released interleukin-1beta (IL-1beta) reaching cerebroventricles stimulates circumventricular organs (CVOs; subfornical organ, SFO; organum vasculosum lamina terminalis, OVLT), the median preoptic nucleus (MePO), and magnocellular and parvocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. Hypertonic saline (HS) also activates these osmosensory CVOs and neuroendocrine systems, but, in contrast to IL-1beta, inhibits the peripheral immune response. To examine whether the brain's innate immune response is attenuated by osmotic stimulation, sterile acidic perfusion fluid was microdialyzed (2 microl/min) in the SON area of conscious rats for 6 h with sterile HS (1.5 M NaCl) injected subcutaneously (15 ml/kg) at 5 h. Immunohistochemistry identified cytokine sources (IL-1beta(+); OX-42(+) microglia) and targets (IL-1R(+); inducible cyclooxygenase, COX-2(+); c-Fos(+)) near the probe, in CVOs, MePO, ependymal cells, periventricular hypothalamus, SON, and PVN. Inserting the probe stimulated magnocellular neurons (c-Fos(+); SON; PVN) via the MePO (c-Fos(+)), a response enhanced by HS. Microdialysis activated microglia (OX-42(+); amoeboid/hypertrophied; IL-1beta(+)) in the adjacent SON and bilaterally in perivascular areas of the PVN, periventricular hypothalamus and ependyma, coincident with c-Fos expression in ependymal cells and COX-2 in the vasculature. These microglial responses were attenuated by HS, coincident with activating parvocellular and magnocellular neuroendocrine systems and elevating circulating IL-1beta, oxytocin, and vasopressin. Acidosis-induced cellular injury from microdialysis activated the brain's innate immune response by a mechanism inhibited by peripheral osmotic stimulation.
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PMID:Peripheral osmotic stimulation inhibits the brain's innate immune response to microdialysis of acidic perfusion fluid adjacent to supraoptic nucleus. 1975 33

Sepsis is physiologically viewed as a proinflammatory and procoagulant response to invading pathogens. There are three recognized stages in the inflammatory response with progressively increased risk of end-organ failure and death: sepsis, severe sepsis, and septic shock. Patients with cirrhosis are prone to develop sepsis, sepsis-induced organ failure, and death. There is evidence that in cirrhosis, sepsis is accompanied by a markedly imbalanced cytokine response ("cytokine storm"), which converts responses that are normally beneficial for fighting infections into excessive, damaging inflammation. Molecular mechanisms for this excessive proinflammatory response are poorly understood. In patients with cirrhosis and severe sepsis, high production of proinflammatory cytokines seems to play a role in the worsening of liver function and the development of organ/system failures such as shock, renal failure, acute lung injury or acute respiratory distress syndrome, coagulopathy, or hepatic encephalopathy. In addition, these patients may have sepsis-induced hyperglycemia, defective arginine-vasopressin secretion, adrenal insufficiency, or compartmental syndrome. In patients with cirrhosis and spontaneous bacterial peritonitis (SBP), early use of antibiotics and intravenous albumin administration decreases the risk for developing renal failure and improves survival. There are no randomized studies that have been specifically performed in patients with cirrhosis and severe sepsis to evaluate treatments that have been shown to improve outcome in patients without cirrhosis who have severe sepsis or septic shock. These treatments include recombinant human activated C protein and protective-ventilation strategy for respiratory failure. Other treatments should be evaluated in the cirrhotic population with severe sepsis including the early use of antibiotics in "non-SBP" infections, vasopressor therapy, hydrocortisone, renal-replacement therapy and liver support systems, and selective decontamination of the digestive tract or oropharynx.
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PMID:Severe sepsis in cirrhosis. 2037 75

Animal studies have implicated oxytocin and vasopressin in social bonding, physiological stress responses, and wound healing. In humans, endogenous oxytocin and vasopressin levels covary with perceptions of relationship quality, marital behaviors, and physiological stress responses. To investigate relationships among marital behavior, oxytocin, vasopressin, and wound healing, and to determine the characteristics of individuals with the highest neuropeptide levels, 37 couples were admitted for a 24-h visit in a hospital research unit. After small blister wounds were created on their forearm, couples participated in a structured social support interaction task. Blister sites were monitored daily following discharge to assess wound repair speed. Blood samples were collected for oxytocin, vasopressin, and cytokine analyses. Higher oxytocin levels were associated with more positive communication behaviors during the structured interaction task. Furthermore, individuals in the upper oxytocin quartile healed blister wounds faster than participants in lower oxytocin quartiles. Higher vasopressin levels were related to fewer negative communication behaviors and greater tumor necrosis factor-alpha production. Moreover, women in the upper vasopressin quartile healed the experimental wounds faster than the remainder of the sample. These data confirm and extend prior evidence implicating oxytocin and vasopressin in couples' positive and negative communication behaviors, and also provide further evidence of their role in an important health outcome, wound healing.
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PMID:Marital behavior, oxytocin, vasopressin, and wound healing. 2014 9

In patients with community-acquired pneumonia, traditional criteria of infection based on clinical signs and symptoms, clinical scoring systems, and general inflammatory indicators (for example, leukocytosis, fever, C-reactive protein and blood cultures) are often of limited clinical value and remain an unreliable guide to etiology, optimal therapy and prognosis. Procalcitonin is superior to other commonly used markers in its specificity for bacterial infection (allowing alternative diagnoses to be excluded), as an indicator of disease severity and risk of death, and mainly as a guide to the necessity for antibiotic therapy. It can therefore be viewed as a diagnostic, prognostic, and perhaps even theragnostic test. It more closely matches the criteria for usefulness than other candidate biomarkers such as C-reactive protein, which is rather a nonspecific marker of acute phase inflammation, and proinflammatory cytokines such as plasma IL-6 levels that are highly variable, cumbersome to measure, and lack specificity for systemic infection. Elevated levels of pro-adrenomedullin, copeptin (which is produced in equimolar amounts to vasopressin), natriuretic peptides and cortisol are significantly related to mortality in community-acquired pneumonia, as are other prohormones such as pro-atrial natriuretic peptide, coagulation markers, and other combinations of inflammatory cytokine profiles. However, all biomarkers have weaknesses as well as strengths. None should be used on its own; and none is anything more than an aid in the exercise of clinical judgment based upon a synthesis of available clinical, physiologic and laboratory features in each patient.
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PMID:Clinical review: the role of biomarkers in the diagnosis and management of community-acquired pneumonia. 2023 71

An emerging literature attests to the ability of psychological stress to alter the inflammatory cytokine environment of the body. While the ability of stress to cause cytokine release is well established, the neural pathways involved in this control have yet to be identified. This study tests the hypothesis that IL-6 neurons of the hypothalamo-neurohypophyseal system (HNS), a neural pathway proposed to secrete IL-6 into the circulation, are activated in response to psychological stress. Colocalization studies confirm robust expression of IL-6 in cell bodies and fibers of vasopressin (but not oxytocin) neurons of the paraventricular (PVN) and supraoptic nucleus (SON) of the rat hypothalamus. In response to restraint, there was a greater increase in c-Fos expression in SON IL-6-positive (IL-6+) neurons. In addition, both psychogenic (restraint) or systemic stress (hypoxia) lead to phosphorylated ERK induction only in IL-6+ magnocellular neurons, indicating selective activation of the MAPK signaling pathway in the IL-6 subset of magnocellular neurons. Finally, restraint upregulated IL-6 mRNA expression in both the PVN and SON, which was accompanied by a four-fold increase in circulating IL-6. The data indicate that noninflammatory stressors selectively activate IL-6 magnocellular neurons, upregulate IL-6 gene expression in the PVN and SON, and increase plasma IL-6. In summary, results show that IL-6 neurons of the HNS are a recruited component of the response to psychological stress.
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PMID:Stress activation of IL-6 neurons in the hypothalamus. 2042 20


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