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)

The hypothalamo-neurohypophysial system contains high levels of neuronal nitric oxide synthase and this increases further during times of neurohormone demand, such as that following osmotic stimulation. Using double in situ hybridization, we demonstrate here an increase in the expression of nitric oxide synthase messenger RNA by oxytocin neurons, but not vasopressin neurons, of the supraoptic nucleus at the time of lactation, when oxytocin is in demand due to another neuroendocrine stimulus, the milk-ejection reflex. In addition, using immunocytochemical retrograde tracing, we show that neurons of the subfornical organ, median preoptic nucleus and organum vasculosum of the lamina terminalis, which project to the supraoptic nucleus, contain nitric oxide synthase. These three structures of the lamina terminalis, together with the hypothalamo-neurohypophysial system, make up the forebrain osmoresponsive circuit that controls osmotically-stimulated release of oxytocin in the rat. The expression of nitric oxide synthase messenger RNA in the lamina terminalis was also shown to increase during lactation. The increases in nitric oxide synthase messenger RNA were not apparent during pregnancy. These results provide evidence for an integrated nitric oxide synthase-containing neural network involved in the regulation of the hypothalamo-neurohypophysial axis. The expression of nitric oxide synthase messenger RNA increases in this circuit during lactation and correlates with a reduction in the sensitivity of the circuit to osmotic stimuli also present in lactation but not pregnancy. As nitric oxide is believed to attenuate neurohormone release, it seems that the increased nitric oxide synthase messenger RNA expression detected here during lactation at a time of high oxytocin demand may be involved in reducing the sensitivity of the whole forebrain circuit to osmotic stimuli.
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PMID:Up-regulation of nitric oxide synthase messenger RNA in an integrated forebrain circuit involved in oxytocin secretion. 904 72

The distribution of immunoreactivity to neuronal nitric oxide synthase (nNOS) and vasopressin (AVP) was studied in the circumventricular organs of the female rat. The occurrence of NOS immunoreactivity showed correspondence to nicotinamide dinucleotide phosphate diaphorase reactivity, a previously used but less specific marker for neuronal NOS. nNOS immunolabeling was detected in the two most rostrally located circumventricular organs - the organum vasculosum of the lamina terminalis and the subfornical organ. In the latter, AVP immunoreactivity was observed in some cell bodies, which also were nNOS-immunoreactive. In the median eminence and the neurohypophysis there were large amounts of nNOS- and AVP-immunoreactive nerve fibers, which often displayed similarities in distribution and morphology. Within the pineal gland, only very few nNOS-immunoreactive varicose terminals were observed, which ran along blood vessels. nNOS immunoreactivity was also seen in the epithelium of the choroid plexus, whereas no nNOS immunoreactivity could be found in the subcommissural organ or in the area postrema. The present demonstration of nNOS and AVP immunoreactivity in the subfornical organ, median eminence, and neurohypophysis, and the occurrence of nNOS immunoreactivity also in the choroid plexus and organum vasculosum of the lamina terminalis, provides a morphological background for a functional role for nitric oxide in water homeostatic mechanisms, both as executed through the hypothalamohypophyseal system and via the production of cerebrospinal fluid.
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PMID:Nitric oxide synthase and vasopressin in rat circumventricular organs. An immunohistochemical study. 938 4

The role played by nitric oxide (NO) and carbon monoxide (CO) was explored in the adult male rat by determining whether antagonizing the activity of the enzymes responsible for the formation of these gases altered the response of the hypothalamic-pituitary-adrenal (HPA) axis to immune (cytokines) or nonimmune (mild electroshocks) signals. The arginine derivative Nomeganitro-L-arginine-methylester (L-NAME), which inhibits all three NO synthase (NOS) isoforms [inducible (i), endothelial (e) and neuronal (n)] significantly augments the ACTH response to blood-borne cytokines, but decreases it in rats exposed to shocks or other physico-emotional stresses. The effect of L-NAME in both models is mimicked by L-nitroarginine (L-NNA) and L-nitromethylarginine (L-NMMA), which block constitutive (e and n) forms of NOS, but not by aminoguanidine (which blocks iNOS) or 7-nitroindazole (which specifically blocks nNOS). Despite the ability of L-NAME to markedly augment the stimulatory effect of vasopressin on ACTH secretion, removal of this peptide does not interfere with the interaction between L-NAME and systemically administered interleukin-1beta (IL-1beta). In contrast, blockade of prostaglandin formation prevents both the stimulatory effect of IL-1beta on ACTH release, and its potentiation by L-NAME. In contrast to the investigation of the importance of endogenous NO, studies focused on the role of CO remain scarce. Our preliminary results suggest that while blockade of the formation of this gas decreases the ACTH response to various stimuli, it also significantly interferes with the effect of L-NAME in rats systemically administered cytokines, and further decreases the ACTH response to shocks in animals also injected with arginine analogs. These results indicate the possible presence of functional interactions between NO and CO in regulating the activity of the HPA axis. Our present working hypothesis is that in the presence of elevated circulating cytokine levels, endogenous NO acts presynaptically to inhibit the release of ACTH secretagogues from nerve terminals in the infundibulum. As the acute ACTH response to these immune proteins is believed to primarily depend on events taking place within the median eminence, blockade of NO formation results in exaggerated ACTH release. During exposure to shocks and other nonimmune stresses, on the other hand, increased ACTH secretion is primarily due to activation of hypothalamic neurons. In this case, because of the stimulatory influence of endogenous NO on hypothalamic perikarya that manufacture corticotropin-releasing factor (CRF) and/or of the afferents to these neurons, blockade of NOS activity blunts CRF production, and consequently ACTH release. What remains undetermined is the net effect of the opposite influences of NO during long-term exposure to immune or nonimmune stress. Finally, it is possible that the conflicting results reported by investigators who study the role of NO and CO in isolated cell preparations may reflect, at least in part, these opposite effects of NO on different elements of the HPA axis.
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PMID:Role of nitric oxide and carbon monoxide in modulating the ACTH response to immune and nonimmune signals. 973 Jun 87

The gas nitric oxide is a messenger in brain signaling. In the hypothalamo-hypophyseal system nitric oxide is involved in the control of the expression and/or release of peptide hormones (corticotropin-releasing hormone, gonadotropin-releasing hormone, vasopressin and oxytocin). Nitric oxide synthase (NOS), the enzyme generating nitric oxide, is abundantly present in the magnocellular nuclei of the rat hypothalamus. Its localization in the human hypothalamus is less well studied. Hence, we investigated the anatomical distribution of neuronal nitric oxide synthase in the human supraoptic nucleus by use of immunohistochemical and enzyme histochemical techniques. The immunohistochemical localization of NOS was studied in 31 matched human hypothalami (13 control cases, eight depressed patients and ten schizophrenics). NADPH-diaphorase studies were carried out on seven additional hypothalami (three normal brains, four schizophrenics). Apparent inter-individual differences exist with regard to the occurrence of the enzyme in supraoptic neurons. In a majority of cases no immunostaining or histochemical reaction for the enzyme was observed. In seven cases (three controls, two schizophrenics, two depressives) a population of nitrergic nerve cells was seen in the dorsomedial part of the nucleus. This group of cells also stained for NADPH-diaphorase. Also, there were a few NOS-immunopositive neurons scattered throughout the nucleus. Additionally, thin NADPH-diaphorase positive fibers were observed to cross the nucleus. Our data show that, unlike the rat, the human supraoptic nucleus contains only a small number of nitrergic neurons. No correlation was found between the expression of the enzyme in supraoptic neurons and the psychiatric status of the patients.
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PMID:Low and infrequent expression of nitric oxide synthase/NADPH-diaphorase in neurons of the human supraoptic nucleus: a histochemical study. 1111 9

Nitric oxide (NO) is known to regulate the release of arginine-vasopressin (AVP) and oxytocin (OT) by the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). The aim of the current study was to identify in these nuclei the NO-producing neurons and the NO-receptive cells in mice. The determination of NO-synthesizing neurons was performed by double immunohistochemistry for the neuronal form of NO synthase (NOS), and AVP or OT. Besides, we visualized the NO-receptive cells by detecting cyclic GMP (cGMP), the major second messenger for NO, by immunohistochemistry on hypothalamus slices. Neuronal NOS was exclusively colocalized with OT in the PVN and the SON, suggesting that NO is mainly synthesized by oxytocinergic neurons in mice. By contrast, cGMP was not observed in magnocellular neurons, but in GABA-, tyrosine hydroxylase- and glutamate-positive fibers, as well as in GFAP-stained cells. The cGMP-immunostaining was abolished by incubating brain slices with a NOS inhibitor (L-NAME). Consequently, we provide the first evidence that NO could regulate the release of AVP and OT indirectly by modulating the activity of the main afferents to magnocellular neurons rather than by acting directly on magnocellular neurons. Moreover, both the NADPH-diaphorase activity and the mean intensity of cGMP-immunofluorescence were increased in monoamine oxidase A knock-out mice (Tg8) compared to control mice (C3H) in both nuclei. This suggests that monoamines could enhance the production of NO, contributing by this way to the fine regulation of AVP and OT release and synthesis.
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PMID:The effects of nitric oxide on magnocellular neurons could involve multiple indirect cyclic GMP-dependent pathways. 1258 Nov 64

Neurons of the hypothalamo-neurohypophyseal system (HNS) are known to contain high amounts of neuronal nitric oxide (NO) synthase (nNOS). NO produced by those neurons is commonly supposed to be involved as modulator in the release of the two nonapeptides vasopressin (AVP) and oxytocin into the blood stream. Previous studies showed that forced swimming fails to increase the release of AVP into the blood stream while its secretion into the hypothalamus is triggered. We investigated here whether hypothalamically acting NO contributes to the control of the AVP release into blood under forced swimming conditions. Intracerebral microdialysis and in situ hybridization were employed to analyze the activity of the nitrergic system within the supraoptic nucleus (SON), the hypothalamic origin of the HNS. A 10-min forced swimming session failed to significantly alter the local NO release as indicated both by nitrite and, the main by-product of NO synthesis, citrulline levels in microdialysis samples collected from the SON. Microdialysis administration of NO directly into the SON increased the concentration of AVP in plasma samples collected during simultaneous forced swimming. In an additional experiment the effect of the defined stressor exposure on the concentration of mRNA coding for nNOS within the SON was investigated by in situ hybridization. Forced swimming increased the expression of nNOS mRNA at two and four hours after onset of the stressor compared to untreated controls. Taken together, our results imply that NO within the SON does not contribute to the regulation of the secretory activity of HNS neurons during acute forced swimming. Increased nNOS mRNA in the SON after forced swimming and the increase in AVP release in the presence of exogenous NO under forced swimming points to a possible role of NO in the regulation of the HNS under repeated stressor exposure.
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PMID:Nitric oxide is not involved in the control of vasopressin release during acute forced swimming in rats. 1475 14

Nitric oxide (NO) is a key activity-dependent modulator of the magnocellular neurosecretory system (MNS) during conditions of high hormonal demand. In addition, recent studies support the presence of a functional constitutive NO tone. The aim of this study was to identify the cellular sources, targets, signalling mechanisms and functional relevance of constitutive NO production within the supraoptic nucleus (SON). Direct visualization of intracellular NO, along with neuronal nitric oxide synthase (nNOS) and cGMP immunohistochemistry, was used to study the cellular sources and targets of NO within the SON, respectively. Our results support the presence of a strong NO basal tone within the SON, and indicate that vasopressin (VP) neurones constitute the major neuronal source and target of basal NO. NO induced-fluorescence and cGMP immunoreactivity (cGMPir) were also found in the glia and microvasculature of the SON, suggesting that they contribute as sources/targets of NO within the SON. cGMPir was also found in association with glutamic acid decarboxylase 67 (GAD67)- and vesicular glutamate transporter 2 (VGLUT2)-positive terminals. Glutamate, acting on NMDA and possibly AMPA receptors, was found to be an important neurotransmitter driving basal NO production within the SON. Finally, electrophysiological recordings obtained from SON neurones in a slice preparation indicated that constitutive NO efficiently restrains ongoing firing activity of these neurones. Furthermore, phasically active (putative VP) and continuously firing neurones appeared to be influenced by NO originating from different sources. The potential roles for basal NO as an autocrine signalling molecule, and one that bridges neuronal-glial-vascular interactions within the MNS are discussed.
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PMID:Cellular sources, targets and actions of constitutive nitric oxide in the magnocellular neurosecretory system of the rat. 1555 Apr 58

Previous studies revealed that the brain angiotensinergic, vasopressinergic and nitrergic systems are involved in regulation of blood pressure and that their function is altered in various forms of hypertension. The purpose of our investigation was to determine whether expression of AT1a angiotensin receptors (AT1aR) mRNA, V1a vasopressin receptors (V1aR) mRNA and neuronal nitric oxide synthase (NOS1) mRNA is altered in the brain of rats with the renovascular hypertension. Eight male Sprague Dawley (SD 2K,1C) rats were subjected to constriction of the left renal artery in order to produce the renovascular hypertension whereas nine SD rats underwent the sham surgery. In both groups blood pressure was determined before and after the surgery. Four weeks after the surgery the brain fragments were harvested for determination of mRNA expression. Competitive PCR method was applied for relative quantitative analysis of V1aR mRNA, AT1aR mRNA and NOS1 mRNA in the preoptic, diencephalic, mesencephalopontine, medullary and cerebellar fragments of the brain. Blood pressure was significantly higher in the 2K,1C than in the sham operated rats. In the preoptic, mesencephalopontine and medullary regions AT1aR mRNA expression was significantly lower in the 2K,1C rats than in the sham operated rats. The 2K,1C rats manifested also significantly higher expression of V1aR mRNA and NOS1 mRNA in the preoptic brain region in comparison to the sham operated rats. The study provides evidence for significant changes of expression of AT1aR mRNA, V1aR mRNA and NOS1 mRNA in the specific brain regions of rats with the renovascular hypertension.
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PMID:Altered expression of angiotensin AT1a and vasopressin V1a receptors and nitric oxide synthase mRNA in the brain of rats with renovascular hypertension. 1561 39

The effects of neuronal, endothelial, or inducible nitric oxide synthase gene disruption on the expression of oxytocin and vasopressin gene were examined in the hypothalamus (paraventricular, supraoptic, suprachiasmatic, and anterior commissural nuclei) and extrahypothalamus (bed nucleus of the stria terminalis). The oxytocin messenger RNA levels in the anterior commissural nucleus of neuronal nitric oxide synthase knockout mice were significantly higher than in control mice, but not in endothelial or inducible nitric oxide synthase knockout mice. In contrast, no significant effects of neuronal, endothelial, or inducible nitric oxide synthase gene disruption on oxytocin and vasopressin messenger RNA levels in the other hypothalamic and extrahypothalamic nuclei were observed. These results suggest that neuronal nitric-oxide-synthase-derived nitric oxide may be involved in the regulation of oxytocin gene expression in the anterior commissural nucleus.
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PMID:Effects of nitric oxide synthase isoform deletion on oxytocin and vasopressin messenger RNA in mouse hypothalamus. 1572 48

Endothelin 1 (ET-1) injected into the lateral cerebral ventricle increases sympathetic output, arterial pressure and plasma vasopressin (AVP). These responses are mediated by glutamatergic inputs and inhibited by gamma-amino-butyric acidergic inputs in the paraventricular nucleus (PVN). It has been suggested that nitric oxide enhances these gamma-amino-butyric acidergic inhibitory inputs. The present studies were designed to test the hypothesis that decreasing neuronal nitric oxide synthase (nNOS) activity within the PVN will potentiate ET-1-induced increases in arterial pressure and alter plasma AVP secretion. Male Long Evans rats underwent adenoviral gene transfer of beta-galactosidase, Ad.CMV.beta-gal (6.25 x 10(4) pfu/PVN; control, n = 5) or injection with DNA plasmids encoding dominant-negative forms of nNOS (RSV hemedomain or RSV heme-RedF; mutant, n = 5) having < 8% normal catalytic activity into the PVN bilaterally. Five days post-injection, the baseline mean arterial pressure in conscious rats was similar in both groups: control, 130 +/- 5 mmHg versus mutant, 122 +/- 6 mmHg. The latency of the pressor response observed after lateral cerebral ventricle injection of 10 pmol ET-1 was 4.8 minutes in controls compared with < 1.5 minutes in rats injected with the mutant nNOS (P < 0.05). After ET-1 administration, the average rise in mean arterial pressure was significantly higher in the nNOS mutant group at 1-2 minutes (16.2 +/- 3.5 mmHg versus -0.6 +/- 4.1 mmHg; P < 0.05) as well as 7-10 minutes later (20.2 +/- 5.1 mmHg versus 8 +/- 2.5 mmHg; P < 0.05). Plasma AVP increased from 2.9 +/- 0.7 pg/mL to 11.5 +/- 1.9 pg/mL in controls (P < 0.004) versus 0.3 +/- 0.2 pg/mL to 1.5 +/- 0.9 pg/mL in the mutant group after ET-1. When the residual effect of nitric oxide generated by other nitric oxide synthase isoforms was assessed by injection of 200 microg Nomega-nitro-L-arginine methyl ester bilaterally into the PVN, the mean arterial pressure increased by 12.2 +/- 2.7 mmHg in controls but was almost unchanged in the mutant group (1.8 +/- 2.4 mmHg; P < 0.025 versus control). These results are consistent with the hypothesis that nitric oxide generated by nNOS within the PVN mediates the inhibition of the pressor response to lateral cerebral ventricle ET-1 and that the greater pressor response seen with the dominant-negative nNOS contructs prevents the rise in plasma AVP in baroreflex-intact rats.
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PMID:Neuronal nitric oxide synthase activity in the paraventricular nucleus buffers central endothelin-1- induced pressor response and vasopressin secretion. 1583 2


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