Control Of Body Fluid Homeostasis Research Articles

Glucocorticoids Reverse Diluted Hyponatremia Through Inhibiting Arginine Vasopressin Pathway in Heart Failure Rats.

BackgroundArginine vasopressin dependent antidiuresis plays a key role in water‐sodium retention in heart failure. In recent years, the role of glucocorticoids in the control of body fluid homeostasis has been extensively investigated. Glucocorticoid deficiency can activate V2R (vasopressin receptor 2), increase aquaporins expression, and result in hyponatremia, all of which can be reversed by glucocorticoid supplement.Methods and ResultsHeart failure was induced by coronary artery ligation for 8 weeks. A total of 32 rats were randomly assigned to 4 groups (n=8/group): sham surgery group, congestive heart failure group, dexamethasone group, and dexamethasone in combination with glucocorticoid receptor antagonist RU486 group. An acute water loading test was administered 6 hours after drug administration. Left ventricular function was measured by a pressure‐volume catheter. Protein expressions were determined by immunohistochemistry and immunoblotting. The pressure‐volume loop analysis showed that dexamethasone improves cardiac function in rats with heart failure. Western blotting confirmed that dexamethasone remarkably reduces the expressions of V2R, aquaporin 2, and aquaporin 3 in the renal‐collecting ducts. As a result of V2R downregulation, the expressions of glucocorticoid regulated kinase 1, apical epithelial sodium channels, and the furosemide‐sensitive Na‐K‐2Cl cotransporter were also downregulated. These favorable effects induced by dexamethasone were mostly abolished by the glucocorticoid receptor inhibitor RU486, indicating that the aforementioned effects are glucocorticoid receptor mediated.ConclusionsGlucocorticoids can reverse diluted hyponatremia via inhibiting the vasopressin receptor pathway in rats with heart failure.

Gaseous Modulators in the Control of the Hypothalamic Neurohypophyseal System

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are gaseous molecules produced by the brain. Within the hypothalamus, gaseous molecules have been highlighted as autocrine and paracrine factors regulating endocrine function. Therefore, in the present review, we briefly discuss the main findings linking NO, CO, and H2S to the control of body fluid homeostasis at the hypothalamic level, with particular emphasis on the regulation of neurohypophyseal system output.

Role of α2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

Mapping and signaling of neural pathways involved in the regulation of hydromineral homeostasis

Several forebrain and brainstem neurochemical circuitries interact with peripheral neural and humoral signals to collaboratively maintain both the volume and osmolality of extracellular fluids. Although much progress has been made over the past decades in the understanding of complex mechanisms underlying neuroendocrine control of hydromineral homeostasis, several issues still remain to be clarified. The use of techniques such as molecular biology, neuronal tracing, electrophysiology, immunohistochemistry, and microinfusions has significantly improved our ability to identify neuronal phenotypes and their signals, including those related to neuron-glia interactions. Accordingly, neurons have been shown to produce and release a large number of chemical mediators (neurotransmitters, neurohormones and neuromodulators) into the interstitial space, which include not only classic neurotransmitters, such as acetylcholine, amines (noradrenaline, serotonin) and amino acids (glutamate, GABA), but also gaseous (nitric oxide, carbon monoxide and hydrogen sulfide) and lipid-derived (endocannabinoids) mediators. This efferent response, initiated within the neuronal environment, recruits several peripheral effectors, such as hormones (glucocorticoids, angiotensin II, estrogen), which in turn modulate central nervous system responsiveness to systemic challenges. Therefore, in this review, we shall evaluate in an integrated manner the physiological control of body fluid homeostasis from the molecular aspects to the systemic and integrated responses.

Apelin in the Control of Body Fluid Homeostasis and Cardiovascular Functions

The discovery of apelin, an endogenous ligand of the orphan APJ receptor is an important advance for fundamental research and clinical medicine. Apelin and its receptor have a wide tissue distribution not only in the brain but also in peripheral organs including kidney, heart, vessels, and adipose tissue. Apelin is implicated in many physiological and pathophysiological processes such as the regulation of body fluid homeostasis, cardiovascular functions, glucose homeostasis, cell proliferation, and angiogenesis. This review focuses on, i) the various signaling cascades evoked upon stimulation of the apelin receptor by the different molecular forms of apelin found in vivo, ii) the distribution of apelin and its receptor in the brain and the cardiovascular system, iii) the opposing actions of vasopressin and apelin in the regulation of water balance at the central and kidney levels, and on the cardiovascular system regarding regulation of arterial blood pressure, vascular tone, and cardiac function.

Negative feedforward control of body fluid homeostasis by hepatorenal reflex

The liver, well known for its role in metabolism, clearance and storage can also be regarded as a sensory organ. The liver is an ideal place to monitor the quality and quantity of absorbed substances, because portal blood delivers substances absorbed from the intestine to the liver and these substances circulate in the hepatic vasculature before substances enter the systemic circulation. Sodium (Na(+))-sensitive mechanism exists in the liver; it is stimulated by the increase in Na(+) concentration in the portal vein, and then hepatorenal reflex is triggered. Renal sympathetic nerve activity is reflexively decreased and urinary Na(+) excretion is increased. This Na(+)-sensitive hepatorenal reflex has a significant role in post-prandial natriuresis. However, the long-term role of this reflex in Na(+) homeostasis may be less important, probably because of the desensitization of Na(+)-sensitive mechanisms. Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) is involved in the hepatoportal Na(+)-sensitive mechanism, and NKCC1 expression is reduced if the hepatoportal region is exposed to high Na(+) concentrations for a long time. This situation occurs when animals intake a high-sodium chloride diet for a long time. Liver cirrhosis also impairs the Na(+)-sensitive hepatorenal reflex. Hepatoportal baroreceptor-induced renal sympathetic excitation and the impaired Na(+)-sensitive hepatorenal reflex may partially explain the Na(+) retention in liver cirrhosis.

Central Endogenous Vasopressin Induced by Central Salt‐Loading Participates in Body Fluid Homeostasis through Modulatory Effects on Neurones of the Paraventricular Nucleus in Conscious Rats

Peripherally secreted arginine vasopressin (AVP) plays a role in controlling body fluid homeostasis, and central endogenous AVP acts as a neurotransmitter or neuromodulator. The limbic system, which appears to exert an inhibitory effect on the endocrine hypothalamus, is also innervated by fibres that contain AVP. We examined whether central endogenous AVP is also involved in the control of body fluid homeostasis. To explore this possibility, we examined neuronal activity in the paraventricular nucleus of the hypothalamus (PVN), periventricular parts of the PVN and limbic brain areas, as well as AVP mRNA expression in the PVN and the peripheral secretion of AVP after central salt-loading in rats that had been pretreated i.c.v. with the AVP V(1) receptor antagonist OPC-21268. Neuronal activity in the PVN evaluated in terms of Fos-like immunoreactivity (FLI), especially in the parvocellular subdivisions, was suppressed. On the other hand, FLI was enhanced in the lateral septum, the bed nucleus of the stria terminalis and the anterior hypothalamic area. Similarly, AVP mRNA expression was enhanced in the magnocellular subnucleus of the PVN, despite the lack of a significant difference in the peripheral AVP level between OPC-21268- and vehicle-pretreated groups. We recorded renal sympathetic nerve activity (RSNA) as sympathetic nerve outflow during central salt-loading. The suppression of RSNA was significantly attenuated by i.c.v. pretreatment with OPC-21268. These results suggest that the suppression of RSNA during central salt-loading might be the result of a decrease in neuronal activity in the parvocellular subdivisions of the PVN via the inhibitory action of central endogenous AVP. The parvocellular and magnocellular neurones in the PVN might show different responses to central salt-loading to maintain body fluid homeostasis as a result of the modulatory role of central endogenous AVP.

Ovine fetal hormonal and hypothalamic neuroendocrine responses to maternal water deprivation at late gestation

Angiotensin II (Ang II), aldosterone, and arginine-vasopressin (AVP) are three major neuropeptides or hormones that are important in the control of body fluid regulation. Dehydration during pregnancy induces alterations in maternal–fetal fluid homeostasis. It is still not clear about effects and mechanisms of maternal water deprivation on fetal neuroendocine and hormonal responses. The present study deprived water from pregnant sheep at near-term for 24h and 48h, and determined maternal and fetal blood osmolality and sodium levels before and immediately after water deprivation. Fetal renal excretion and plasma hormones were measured. Fetal forebrain was analyzed for cellular activation marked with Fos and Fos-B. The results showed that maternal and fetal blood osmolality and sodium were increased by water deprivation. Maternal and fetal Ang II, aldosterone, and AVP levels were elevated by 24-h and 48-h water deprivation, while fetal plasma Ang I levels were increased only under the condition of 48-h water deprivation. Intensive Fos and Fos-B expression was detected in the median preoptic nuclei and paraventricular nuclei in the fetal brain following exposure to maternal water deprivation. Double labeling demonstrated that many Fos-positive cells were AVP-containing neurons in the fetal paraventricular nucleus. Together, the results suggest that neuroendocrine and hormonal regulatory mechanisms play a role in the control of body fluid homeostasis, and relatively matured and functional at the last third of gestation, as well as the fetal hypothalamus is functional in the control of the neuropeptide in response to maternal dehydration.

Neuroendocrine regulatory peptide-1 and -2: novel bioactive peptides processed from VGF.

Neuroendocrine regulatory peptides (NERP)-1 and NERP-2 are derived from distinct regions of VGF, a neurosecretory protein that was originally identified as a product of a nerve growth factor-responsive gene in rat PC12 cells. The amino acid length of human NERP-1 is 26, and that of rat NERP-1 is 25. Human and rat NERP-2 are both 38 amino acid peptides. NERPs colocalize with vasopressin in the storage granules of the paraventricular and supraoptic nuclei in the hypothalamus of both rats and humans. Administration of NERPs suppresses hypertonic saline- or angiotensin II-induced vasopressin release from the hypothalamus and pituitary. Thus, VGF is a precursor of multiple bioactive peptides with diverse neuroendocrine functions, and NERPs are novel hypothalamic peptides involved in the control of body fluid homeostasis by regulating vasopressin release.

Central actions of glucocorticoids in the control of body fluid homeostasis: Review

The involvement of the hypothalamic-pituitary-adrenal axis in the control of body fluid homeostasis has been extensively investigated in the past few years. In the present study, we reviewed the recent results obtained using different approaches to investigate the effects of glucocorticoids on the mechanisms of oxytocin and vasopressin synthesis and secretion in response to acute and chronic plasma volume and osmolality changes. The data presented here suggest that glucocorticoids are not only involved in the mechanisms underlying the fast release but also in the transcriptional events that lead to decreased synthesis and secretion of these neuropeptides, particularly oxytocin, under diverse experimental conditions of altered fluid volume and tonicity. The endocannabinoid system, through its effects on glutamatergic neurotransmission within the hypothalamus and the nuclear factor kappaB-mediated transcriptional activity, seems to be also involved in the specific mechanisms by which glucocorticoids exert their central effects on neurohypophyseal hormone synthesis and secretion.

The chemokine SDF-1/CXCL12 and Vasopressin expression in the hypothalamus of Tunisian rodent, Meriones shawi, subjected to water restriction and Cd exposure

Event Abstract Back to Event The chemokine SDF-1/CXCL12 and Vasopressin expression in the hypothalamus of Tunisian rodent, Meriones shawi, subjected to water restriction and Cd exposure Sihem Mbarek1*, Tounes Saidi1, William Rostene2, Stephane Parsandaniantz2 and Rafika B. Chaouacha-Chekir1 1 Institut Superieur de Biotechnologie Sidi Thabet 2020, Laboratoire d'Ecophysiologie Generale et Comparee, Tunisia 2 INSERM-UPMC UMRS 732, Hospital Saint Antoine, France Stromal-cell-derived factor 1 (SDF-1/CXCL12) is a chemokine recently found to be constitutively expressed with it receptor in vasopressinergic neurons in the supraoptic (SON) and the paraventricular nuclei (PVN). The phasic pattern of these neurons facilitates sustained antidiuresis during dehydration. Here, we investigated whether SDF-1 can interact with arginine-vasopressin (AVP) to maintain body fluid homeostasis in a rodent adapted to desert life (Meriones shawi). In order to clarify the implication of SDF-1 in water metabolism regulation, we sought to determine whether SDF-1 colocalized with AVP in both SON and PVN in basal and water dehydration conditions. We also investigated the effects of cadmium (Cd) exposure on the co-expression of SDF-1 and AVP within these two nuclei in different water states. Using dual immunolabeling microscopy, we found that SDF-1-immunoreactive neurons colocalized with AVP within both SON and PVN magnocellular neurons in Meriones shawi. In contrast to what was observed in the laboratory rat where dehydration causes a dramatic depletion of hypothalamic AVP/ SDF-1 immunoreactivity in both SON and PVN, dehydration induced in our model an increase in expression of AVP and SDF-1. Interestingly, we observed that the ability of acute systemic dehydration to produce AVP/SDF-1 in both SON and PVN was also observed by treating Meriones with Cd. However, the co-expression of both AVP and SDF-1 immunoreactivity from dehydrated animals in the presence of Cd was markedly and significantly lower than in the absence of Cd. The present innovative data support the involvement of the chemokine SDF-1 in the control of body fluid homeostasis and suggest that changes in the expression of the SDF-1 appear to be closely linked to changes in AVP immunoreactivity. Acknowledgments: This work was supported by an INSERM-DGRSRT grant and by a grant from the University P and M Curie Paris VI Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Poster Presentation Topic: Aging & Environment Citation: Mbarek S, Saidi T, Rostene W, Parsandaniantz S and Chaouacha-Chekir RB (2009). The chemokine SDF-1/CXCL12 and Vasopressin expression in the hypothalamus of Tunisian rodent, Meriones shawi, subjected to water restriction and Cd exposure. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.185 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 29 Nov 2009; Published Online: 29 Nov 2009. * Correspondence: Sihem Mbarek, Institut Superieur de Biotechnologie Sidi Thabet 2020, Laboratoire d'Ecophysiologie Generale et Comparee, 2092 Tunis, Tunisia, sihemmbarek@yahoo.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sihem Mbarek Tounes Saidi William Rostene Stephane Parsandaniantz Rafika B Chaouacha-Chekir Google Sihem Mbarek Tounes Saidi William Rostene Stephane Parsandaniantz Rafika B Chaouacha-Chekir Google Scholar Sihem Mbarek Tounes Saidi William Rostene Stephane Parsandaniantz Rafika B Chaouacha-Chekir PubMed Sihem Mbarek Tounes Saidi William Rostene Stephane Parsandaniantz Rafika B Chaouacha-Chekir Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Implication of SDF1/CXCL12 in drinking behavior

Event Abstract Back to Event Implication of SDF1/CXCL12 in drinking behavior Sihem Mbarek1* 1 Faculte des Sciences, Universite de Tunis,Sidi Thabet, Institut Superieur de Biotechnologie, Sidi Thabet Technopole, Tunisia Stromal-cell-derived factor 1 (SDF-1/CXCL12) is a chemokine recently found to be constitutively expressed with it receptor in vasopressinergic neurons in the supraoptic (SON) and the paraventricular nuclei (PVN). The phasic pattern of these neurons facilitates sustained antidiuresis during dehydration. Here, we investigated whether SDF-1 can interact with arginine-vasopressin (AVP) to maintain body fluid homeostasis in a rodent adapted to desert life (Meriones shawi). In order to clarify the implication of SDF-1 in water metabolism regulation, we sought to determine whether SDF-1 colocalized with AVP in both SON and PVN in basal and water dehydration conditions. We also investigated the effects of cadmium (Cd) exposure on the co-expression of SDF-1 and AVP within these two nuclei in different water states. Using dual immunolabeling microscopy, we found that SDF-1-immunoreactive neurons colocalized with AVP within both SON and PVN magnocellular neurons in Meriones shawi. In contrast to what was observed in the laboratory rat where dehydration causes a dramatic depletion of hypothalamic AVP/ SDF-1 immunoreactivity in both SON and PVN, dehydration induced in our model an increase in expression of AVP and SDF-1. Interestingly, we observed that the ability of acute systemic dehydration to produce AVP/SDF-1 in both SON and PVN was also observed by treating Meriones with Cd. However, the co-expression of both AVP and SDF-1 immunoreactivity from dehydrated animals in the presence of Cd was markedly and significantly lower than in the absence of Cd. The present innovative data support the involvement of the chemokine SDF-1 in the control of body fluid homeostasis and suggest that changes in the expression of the SDF-1 appear to be closely linked to changes in AVP immunoreactivity. Acknowledgments: This work was supported by an INSERM-DGRSRT grant and by a grant from the University P and M Curie Paris VI. Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Topic: Symposium 17 – Chemokines: new modulators in brain and pituitary functions Citation: Mbarek S (2009). Implication of SDF1/CXCL12 in drinking behavior. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.067 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Nov 2009; Published Online: 20 Nov 2009. * Correspondence: Sihem Mbarek, Faculte des Sciences, Universite de Tunis,Sidi Thabet, Institut Superieur de Biotechnologie, Sidi Thabet Technopole, 2092 Tunis, Tunisia, sihemmbarek@yahoo.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sihem Mbarek Google Sihem Mbarek Google Scholar Sihem Mbarek PubMed Sihem Mbarek Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Modulation of apelin and APJ receptor in normal and preeclampsia-complicated placentas.

Apelin is an endogenous ligand of the human orphan receptor APJ. This peptide is produced through processing from the C-terminal portion in the pre-pro-protein consisting of 77 amino acid residues and exists in multiple molecular forms. Although the main physiological functions of apelin have not yet been clarified, it is known that apelin is involved in the regulation of blood pressure, blood flow and central control of body fluid homeostasis in different organs. Since human placenta is a tissue where vasculogenesis, blood pressure and flow are dramatically important to allow a normal embryonic and fetal growth and development, the aim of the present study was to investigate the immunohistochemical distribution of apelin and APJ in normal placentas throughout pregnancy and in preeclampsia-complicated placentas. Specifically, we observed that in normal placentas the expression levels of apelin decreased from the first to the third trimester of gestation in both cytotrophoblast and syncytiotrophoblast cells and in the stroma of placental villi, in contrast with increased expression levels of APJ in the cytoplasm of cytotrophoblast cells and in the cytoplasm of endothelial cells of normal placenta samples. In contrast, in preeclampsia-complicated pregnancies, we observed a very strong increase of expression levels of both apelin and APJ receptor in all the placental compartments, cytotrophoblast, syncytiotrophoblast and stroma with a particular increase in endothelial cells inside preeclamptic placental villi. Our data seem to indicate an important role of apelin and APJ in the regulation of fetal development through a correct regulation of human placenta formation during pregnancy. Moreover, the strong expression levels of apelin and APJ in preeclamptic placentas, suggest their possible involvement in the onset of this pathology.

Compartmentalization of hypothalamic TRPV4 in lipid rafts in the rat: putative role in the central control of body fluid homeostasis

The molecular mechanisms underlying the osmotic sensitivity of hypothalamic neurons have not been fully described. Recent studies indicate that transient receptor potential (TRP) channels contribute to the intrinsic osmosensitivity of cells from the supraoptic nucleus (SON) and other osmotically sensitive parts of the forebrain. The impaired osmotic regulation in trpv4−/− mice suggests TRPV4 plays a role in osmotic signaling. Using different models of dehydration and bile duct ligations (BDL), a model of hepatic cirrhosis associated with elevated circulating vasopressin with hypo-osmolality, we tested the hypothesis that TRPV4 expression (western blotting) and compartmentalization could be regulated by changes in plasma osmolality. We found increased expression of TRPV4 in SON of 48 h water deprived rats and also in rats given 2% saline to drink for 10 days. The abundance of TRPV4 and nNOS was increased in the SON of BDL rats. Next we hypothesized that compartmentalization of the TRPV4 in the plasma membrane may play a role in its signaling. We have found that TRPV4 associates with lipid rafts (LR) in hypothalamus membranes (HM) from normal rats and a higher abundance of TRPV4 was associated in LR of BDL rats HM. When BDL rats were given 0.9% saline to drink, the abundance of TRPV4 associated with LR in HM returned to the control levels. In conclusion, our data suggest that changes in the expression and compartmentalization of TRPV4 in lipid rafts could alter the intracellular signaling of magnocellular neurons. (NIH HL062579 & DK57822).

Corticotropin-releasing hormone in the lateral parabrachial nucleus inhibits sodium appetite in rats

The present study investigated the role of corticotropin-releasing hormone (CRH) in the lateral parabrachial nucleus (LPBN) in the behavioral control of body fluid homeostasis by determining the effect of bilateral injections of the CRH receptor antagonist, alpha-helical corticotropin-releasing factor (CRF)(9-41), and the CRH receptor agonist, CRH, on sodium chloride (salt appetite) and water (thirst) intake. Groups of adult, male Sprague-Dawley rats had stainless-steel cannulas implanted bilaterally into the LPBN and were sodium depleted or water deprived. Bilateral injections of alpha-helical CRF(9-41) into the LPBN significantly potentiated water and salt intake in the sodium-depleted rats when access to fluids was restored. Bilateral injections of alpha-helical CRF(9-41) into the LPBN (1.0 microg) also increased sodium appetite in water-deprived rats. Conversely, in sodium-depleted animals, bilateral injections of CRH inhibited sodium chloride intake. These results suggest that there is an endogenous CRH inhibitory mechanism operating in the LPBN to modulate the intake of sodium (salt appetite). This mechanism may contribute to the behavioral control of restoration of body fluid homeostasis in sodium-deficient states.

N-Methyl-D-Aspartate Glutamate Receptor Mediates Spontaneous and Angiotensin II-Stimulated Ovine Fetal Swallowing

In adult rats, N-methyl-D-aspartate (NMDA) receptors have been implicated in the central control of body fluid homeostasis, as intracerebroventricular (ICV) injection of NMDA receptor antagonists suppresses stimulated drinking behavior. Fetal swallowing occurs at a significantly higher rate as compared to adult drinking, contributing to amniotic fluid volume regulation and fetal gastrointestinal development. The aim of present study was to determine the role of central NMDA receptors in the modulation of fetal swallowing activity. Eight time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and ICV catheters, electrocorticogram (ECoG), and esophageal electromyogram electrodes and studied at 130 +/- 1 days' gestation. Following an initial 2-hour baseline period (time 2 h), the NMDA receptor antagonist, dizocipline (1 mg), was injected ICV. At time 4 h, the dose of dizocipline was repeated, together with angiotensin II (AngII, 6.4 microg). Fetal swallowing was monitored for 2 hours after each injection. Four of these fetuses also received an identical control study (on an alternate day) in which dizocipline was replaced with artificial cerebrospinal fluid (aCSF). ICV dizocipline injection nearly abolished spontaneous fetal swallowing activities (0.6 +/- 0.1 to 0.2 +/- 0.1 swallows/min; P < .001). ICV AngII in the presence of dizocipline did not demonstrate a dipsogenic effect on fetal swallowing (0.1 +/- 0.1; P < .001). In the control study, ICV injection of aCSF did not change fetal swallowing activity (1.0 +/- 0.1 swallows/min), while ICV AngII resulted in a significant increase in fetal swallowing (2.0 +/- 0.1 swallows/min; P < .001). This study demonstrates that central NMDA-glutamate receptor-mediated activity contributes to the high rate of spontaneous and AngII-stimulated fetal swallowing. We speculate that reduced NMDA receptor expression within the forebrain dipsogenic neurons may account for observed differences in drinking activities between the fetus/neonate and the adult.

Peptide metabolism and the control of body fluid homeostasis.

In this paper, we review our current understanding of the medicinal chemistry of the major peptide systems, which influence body fluid homeostasis. Electrolytes play pivotal roles in intra- and intercellular communication, acid-base equilibrium and, when bound to several macromolecules, they regulate a myriad of enzymatic proteins, receptors and transcription factors. Cell turgor influences the plasma membrane, which activates mechanically-gated ion channels or mechanoreceptors, and the expression of a number of genes which underlie long-term metabolic responses to hormones, substrates and reactive oxygen intermediates. The altered kinetics and enzymatic cleavage of peptides during water-electrolyte imbalance can contribute to cardiac and renal damage associated with elevated blood pressure. Identification of the enzymes which are responsible for cleavage, together with emerging information about the mechanisms of action and structures of regulatory and effector peptides, has laid a foundation for the discovery of novel drugs, some of which are in use or are now undergoing evaluation in experimental trials. The development of models of hydrosaline challenge with relative efficiency to induce selective water-electrolyte imbalance has permitted the identification of kallikrein-kinin, renin-angiotensin-aldosterone, vasopressin-oxytocin, thyrotropin-releasing hormone and luteinizing hormone-releasing hormone as susceptible substrates. At present, the angiotensin-I converting enzyme inhibitors are well-known efficacious, orally active, blood pressure-lowering agents which have been used in hypertensive patients. In addition to several new analogues of this class of drug, some selective dual inhibitors of angiotensin-I converting enzyme and neutral endopeptidase and inhibitors of aminopeptidases are now also being rationally assayed and their beneficial effects on hypertension and hydromineral balance indicate that this type of drug may have powerful therapeutic effects for disorders of body fluid homeostasis.

Distribution of apelin, the endogenous ligand of the APJ receptor, in the lizard Podarcis sicula

Apelin is a novel bioactive peptide that has been isolated from bovine stomach extracts and identified as the endogenous ligand for the APJ receptor. Although the main physiological functions of apelin have not yet been clarified, it is known that apelin is involved in the regulation of blood pressure, central control of body fluid homeostasis and the modulation of immune response. In order to investigate the distribution of apelin in reptiles, we have performed an immunohistochemical analysis on tissues of the lizard Podarcis sicula. The peptide was found to be widely distributed, although its cellular localization differed in the various organs examined. A strong immunopositivity was found in the heart, stomach and intestine. In the spleen, an intense apelin immunopositivity was restricted to a discrete number of cells scattered throughout the red pulp and co-localized with immunoglobulin kappa and lambda chains, suggesting an analogous function of this peptide in immune responses also in reptiles. Intriguingly, apelin immunoreactivity was discretely localized in endothelial cells in the lung and thyroid gland. In the light of these data, we conclude that apelin may have multiple functions in reptiles.

Dehydration-induced cross-regulation of apelin and vasopressin immunoreactivity levels in magnocellular hypothalamic neurons.

Apelin, a neuropeptide recently identified as the endogenous ligand for the G protein-coupled receptor APJ, is highly concentrated in brain structures involved in the control of body fluid homeostasis including the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei. To clarify the implication of apelin in the regulation of water balance, we sought to determine whether apelin colocalized with arginine vasopressin (AVP) in the rat SON and PVN. We also investigated the effects of water deprivation on the levels of apelin within these two nuclei by comparison with those of AVP. Using dual immunolabeling confocal microscopy, we found that a large proportion of apelin-immunoreactive neurons colocalized AVP within both the SON and PVN, but that the two peptides were segregated within distinct subcellular compartments inside these cells. Both the number and labeling intensity of magnocellular apelin-immunoreactive cells increased significantly after 24- or 48-h dehydration, whereas the number and labeling density of AVP-immunoreactive neurons significantly decreased. The dehydration-induced increase in apelin immunoreactivity was markedly diminished by central injection of a selective vasopressin-1 receptor antagonist. Conversely, the effect of dehydration was mimicked by a 16-min intracerebroventricular infusion of AVP, again in a vasopressin-1 receptor antagonist-reversible manner. These results provide additional evidence for the involvement of the neuropeptide apelin in the control of body fluid homeostasis. They further suggest that the dehydration-induced release of AVP from magnocellular hypothalamic neurons may be responsible for the observed increase in immunoreactive apelin levels within the same neurons and thus that the release of one peptide may block that of another peptide synthesized in the same cells.

Neuroendocrine control of body fluid metabolism.

Mammals control the volume and osmolality of their body fluids from stimuli that arise from both the intracellular and extracellular fluid compartments. These stimuli are sensed by two kinds of receptors: osmoreceptor-Na+ receptors and volume or pressure receptors. This information is conveyed to specific areas of the central nervous system responsible for an integrated response, which depends on the integrity of the anteroventral region of the third ventricle, e.g., organum vasculosum of the lamina terminalis, median preoptic nucleus, and subfornical organ. The hypothalamo-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting vasopressin and oxytocin in response to osmotic and nonosmotic stimuli. Since the discovery of the atrial natriuretic peptide (ANP), a large number of publications have demonstrated that this peptide provides a potent defense mechanism against volume overload in mammals, including humans. ANP is mostly localized in the heart, but ANP and its receptor are also found in hypothalamic and brain stem areas involved in body fluid volume and blood pressure regulation. Blood volume expansion acts not only directly on the heart, by stretch of atrial myocytes to increase the release of ANP, but also on the brain ANPergic neurons through afferent inputs from baroreceptors. Angiotensin II also plays an important role in the regulation of body fluids, being a potent inducer of thirst and, in general, antagonizes the actions of ANP. This review emphasizes the role played by brain ANP and its interaction with neurohypophysial hormones in the control of body fluid homeostasis.