scholarly journals Signal Transduction of Mineralocorticoid and Angiotensin II Receptors in the Central Control of Sodium Appetite: A Narrative Review

2021 ◽  
Vol 22 (21) ◽  
pp. 11735
Author(s):  
Michele Iovino ◽  
Tullio Messana ◽  
Giuseppe Lisco ◽  
Aldo Vanacore ◽  
Vito Angelo Giagulli ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Salt Intake ◽  
Sodium Intake ◽  
Zona Glomerulosa ◽  
Narrative Review ◽  
Mitogen Activated Protein Kinase ◽  
Central Control ◽  
Ang Ii ◽  
Sodium Appetite ◽  
Mesh Terms

Sodium appetite is an innate behavior occurring in response to sodium depletion that induces homeostatic responses such as the secretion of the mineralocorticoid hormone aldosterone from the zona glomerulosa of the adrenal cortex and the stimulation of the peptide hormone angiotensin II (ANG II). The synergistic action of these hormones signals to the brain the sodium appetite that represents the increased palatability for salt intake. This narrative review summarizes the main data dealing with the role of mineralocorticoid and ANG II receptors in the central control of sodium appetite. Appropriate keywords and MeSH terms were identified and searched in PubMed. References to original articles and reviews were examined, selected, and discussed. Several brain areas control sodium appetite, including the nucleus of the solitary tract, which contains aldosterone-sensitive HSD2 neurons, and the organum vasculosum lamina terminalis (OVLT) that contains ANG II-sensitive neurons. Furthermore, sodium appetite is under the control of signaling proteins such as mitogen-activated protein kinase (MAPK) and inositol 1,4,5-thriphosphate (IP3). ANG II stimulates salt intake via MAPK, while combined ANG II and aldosterone action induce sodium intake via the IP3 signaling pathway. Finally, aldosterone and ANG II stimulate OVLT neurons and suppress oxytocin secretion inhibiting the neuronal activity of the paraventricular nucleus, thus disinhibiting the OVLT activity to aldosterone and ANG II stimulation.

Angiotensin II-induced thirst, but not sodium appetite, via AT1 receptors in organum cavum prelamina terminalis

1995 ◽  
Vol 268 (6) ◽  
pp. R1401-R1405 ◽  
Author(s):  
M. el Ghissassi ◽  
S. N. Thornton ◽  
S. Nicolaidis
Keyword(s):  
Angiotensin Ii ◽  
Salt Intake ◽  
High Sensitivity ◽  
Ang Ii ◽  
Nacl Solution ◽  
At1 Receptors ◽  
Sodium Appetite ◽  
Specific Antagonist

The angiotensin receptor specificity, with respect to fluid intake, of the organum cavum prelamina terminalis (OCPLT), a recently discovered discrete forebrain structure with high sensitivity to angiotensin II (ANG II), was investigated. ANG II (10 ng) microinjected into the OCPLT significantly increased water consumption but did not induce intake of a hypertonic (3%) NaCl solution. Losartan, an ANG II type 1 (AT1) receptor-specific antagonist, produced dose-related (1-100 ng) inhibition of ANG II-induced drinking. The ANG II type 2 receptor-specific antagonist CGP-42112A was ineffective. Intake of the 3% NaCl solution in response to microinjection of either of the antagonists into the OCPLT was never observed. These findings suggest that water intake produced by microinjection of ANG II into the OCPLT is mediated by AT1 receptors uniquely and that, in contrast to other regions of the brain, these receptors do not induce salt intake when stimulated by ANG II.

Central infusion of the AT1 receptor antagonist losartan inhibits thirst but not sodium appetite in cattle

1997 ◽  
Vol 272 (6) ◽  
pp. R1940-R1945 ◽  
Author(s):  
J. R. Blair-West ◽  
D. A. Denton ◽  
M. J. McKinley ◽  
R. S. Weisinger
Keyword(s):  
Water Intake ◽  
Salt Intake ◽  
Sodium Intake ◽  
High Water ◽  
Salt Appetite ◽  
Ang Ii ◽  
Sodium Depletion ◽  
Water Restriction ◽  
Sodium Appetite ◽  
High Water Intake

Experiments in cattle compared the effects of intracerebroventricular (i.c.v.) infusions of losartan and PD-123319 on water intake caused by water restriction, i.c.v. infusion of hypertonic NaCl, or i.c.v. infusion of angiotensin II (ANG II). The effects of these receptor antagonists on sodium intake caused by sodium depletion were also examined. Losartan infusion caused dose-dependent inhibition of the high water intake caused by the physiological stimulus of water restriction or by ANG II infusion but did not affect salt appetite. PD-123319 infused at equimolar or greater (in ANG II experiments) doses did not affect water intake or salt intake due to sodium depletion. The results of these i.c.v. infusion experiments confirm our earlier proposal that the physiological regulation of water intake in cattle may be mediated by ANG II acting centrally via AT1 receptors. The dose of losartan that inhibited thirst in cattle did not inhibit sodium appetite, nor did an equimolar dose of PD-123319.

Abstract P614: Relationship Of Sodium Intake And Stress With Bone Health In Women

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Allison Jasti ◽  
Deborah L Stewart ◽  
Gregory A Harshfield
Keyword(s):  
Bone Health ◽  
Salt Intake ◽  
Sodium Intake ◽  
Target Organ Damage ◽  
African American Adolescents ◽  
Ang Ii ◽  
Mineral Density ◽  
High Sodium ◽  
Low Sodium ◽  
Relationship Of

Background: The skeleton is vital to sodium homeostasis, accounting for 40% of the body’s sodium. Research indicates stress and low sodium intake are independently associated with RAAS activation. In certain populations, stress can induce salt sensitivity, increasing the risk of hypertension and target organ damage, but the association of low versus high sodium intake with bone health is controversial. Purpose: This study sought out the relationship of low sodium and stress-induced RAAS activation with bone health. The tested hypothesis was those with lowest sodium intake would have lower total bone mineral density (TBMD) and content (TBMC) associated with stress-induced increases in angiotensin ii (Ang II) and aldosterone (Aldo). Methods: We compared effect of stress on Ang II, Aldo, TBMD and TMBC in healthy Caucasian and African-American adolescents. Subjects were grouped by quartiles based on sodium intake, assessed by urinary sodium excretion. Results: Due to females, overall significant inverse associations are observed between TBMD, TBMC, Ang II and Aldo in the lowest sodium intake quartile. Post-stress, women in the lowest sodium intake quartile showed that increases in both Ang II and Aldo correspond with lower TMBC and TMBD. There was no significance between Ang II, Aldo, TMBC and TMBD in the three highest quartiles of women nor in any male quartile. Conclusion: These data suggest Ang II and Aldo may reduce TMBC and TMBD in women. Stress-induced increases in Ang II and Aldo, with low sodium intake, may further reduce TBMD and TBMC in women. Ang II inhibition and/or moderated salt intake may be an efficacious prevention or treatment against the development of osteoporosis.

Angiotensin II early regulated genes in H295R human adrenocortical cells

2004 ◽  
Vol 19 (1) ◽  
pp. 106-116 ◽  
Author(s):  
Damian G. Romero ◽  
Maria Plonczynski ◽  
Gaston R. Vergara ◽  
Elise P. Gomez-Sanchez ◽  
Celso E. Gomez-Sanchez
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Intracellular Signaling ◽  
Zona Glomerulosa ◽  
Ang Ii ◽  
Cellular Functions ◽  
Cellular Mechanisms ◽  
Mediated Effects ◽  
Aldosterone Production ◽  
H295r Cells

Evidence for the dysregulation of aldosterone synthesis in cardiovascular pathophysiology has renewed interest in the control of its production. Cellular mechanisms by which angiotensin II (ANG II) stimulates aldosterone synthesis in the adrenal zona glomerulosa are incompletely understood. To elucidate the mechanism of intracellular signaling by ANG II stimulation in the adrenal, we have studied immediate-early regulated genes in human adrenal H295R cells using cDNA microarrays. H295R cells were stimulated with ANG II for 3 h. Gene expression was analyzed by microarray technology and validated by real-time RT-PCR. Eleven genes were found to be upregulated by ANG II. These encode the proteins for ferredoxin, Nor1, Nurr1, c6orf37, CAT-1, A20, MBLL, M-Ras, RhoB, GADD45α, and a novel protein designated FLJ45273 . Maximum expression levels for all genes occurred 3–6 h after ANG II stimulation. This increase was dose dependent and preceded maximal aldosterone production. Other aldosterone secretagogues, K+and endothelin-1 (ET-1), also induced the expression of these genes with variable efficiency depending on the gene and with lower potency than ANG II. ACTH had negligible effect on gene expression except for the CAT-1 and Nurr1 genes. These ANG II-stimulated genes are involved in several cellular functions and are good candidate effectors and regulators of ANG II-mediated effects in adrenal zona glomerulosa.

Angiotensin II regulates phosphorylation of translation elongation factor-2 in cardiac myocytes

2001 ◽  
Vol 281 (1) ◽  
pp. H161-H167 ◽  
Author(s):  
Allen D. Everett ◽  
Tamara D. Stoops ◽  
Angus C. Nairn ◽  
David Brautigan
Keyword(s):  
Protein Synthesis ◽  
Angiotensin Ii ◽  
Cardiac Myocytes ◽  
Elongation Factor ◽  
Protein Translation ◽  
Mitogen Activated Protein Kinase ◽  
Ang Ii ◽  
Elongation Factor 2 ◽  
Mitogen Activated Protein ◽  
20 Nm

Increased protein synthesis is the cardinal feature of cardiac hypertrophy. We have studied angiotensin II (ANG II)-dependent regulation of eukaryotic elongation factor-2 (eEF-2), an essential component of protein translation required for polypeptide elongation, in rat neonatal cardiac myocytes. eEF2 is fully active in its dephosphorylated state and is inhibited following phosphorylation by eEF2 kinase. ANG II treatment (10−10–10−7 M) for 30 min produced an AT1 receptor-specific and concentration- and time-dependent reduction in the phosphorylation of eEF-2. Protein phosphatase 2A (PP2A) inhibitors okadaic acid and fostriecin, but not the PP2B inhibitor FK506, attenuated ANG II-dependent dephosphorylation of eEF-2. ANG II activated mitogen-activated protein kinase, (MAPK) within 10 min of treatment, and blockade of MAPK activation with PD-98059 (1–20 nM) inhibited eEF-2 dephosphorylation. The effect of ANG II on eEF-2 dephosphorylation was also blocked by LY-29004 (1–20 nM), suggesting a role for phosphoinositide 3-kinase, but the mammalian target rapamycin inhibitor rapamycin (10–100 nM) had no effect. Together these results suggest that the ANG II-dependent increase in protein synthesis includes activation of eEF-2 via dephosphorylation by PP2A by a process that involves both PI3K and MAPK.

scholarly journals Central and peripheral slow-pressor mechanisms contributing to Angiotensin II-salt hypertension in rats

2017 ◽  
Vol 114 (2) ◽  
pp. 233-246 ◽  
Author(s):  
Jiao Lu ◽  
Hong-Wei Wang ◽  
Monir Ahmad ◽  
Marzieh Keshtkar-Jahromi ◽  
Mordecai P Blaustein ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Cortex ◽  
Salt Intake ◽  
Plasma Corticosterone ◽  
High Salt ◽  
Ang Ii ◽  
Intracerebroventricular Infusion ◽  
High Salt Intake ◽  
Endogenous Ouabain ◽  
Salt Hypertension

AbstractAimsHigh salt intake markedly enhances hypertension induced by angiotensin II (Ang II). We explored central and peripheral slow-pressor mechanisms which may be activated by Ang II and salt.Methods and resultsIn protocol I, Wistar rats were infused subcutaneously with low-dose Ang II (150 ng/kg/min) and fed regular (0.4%) or high salt (2%) diet for 14 days. In protocol II, Ang II-high salt was combined with intracerebroventricular infusion of mineralocorticoid receptor (MR) blockers (eplerenone, spironolactone), epithelial sodium channel (ENaC) blocker (benzamil), angiotensin II type 1 receptor (AT1R) blocker (losartan) or vehicles. Ang II alone raised mean arterial pressure (MAP) ∼10 mmHg, but Ang II-high salt increased MAP ∼50 mmHg. Ang II-high salt elevated plasma corticosterone, aldosterone and endogenous ouabain but not Ang II alone. Both Ang II alone and Ang II-high salt increased mRNA and protein expression of CYP11B2 (aldosterone synthase gene) in the adrenal cortex but not of CYP11B1 (11-β-hydroxylase gene). In the aorta, Ang II-high salt increased sodium-calcium exchanger-1 (NCX1) protein. The Ang II-high salt induced increase in MAP was largely prevented by central infusion of MR blockers, benzamil or losartan. Central blockades significantly lowered plasma aldosterone and endogenous ouabain and markedly decreased Ang II-high salt induced CYP11B2 mRNA expression in the adrenal cortex and NCX1 protein in the aorta.ConclusionThese results suggest that in Ang II-high salt hypertension, MR-ENaC-AT1R signalling in the brain increases circulating aldosterone and endogenous ouabain, and arterial NCX1. These factors can amplify blood pressure responses to centrally-induced sympatho-excitation and thereby contribute to severe hypertension.

Control of adrenal cell proliferation by AT1 receptors in response to angiotensin II and low-sodium diet

1999 ◽  
Vol 276 (2) ◽  
pp. E303-E309 ◽  
Author(s):  
Pauline E. McEwan ◽  
Gavin P. Vinson ◽  
Christopher J. Kenyon
Keyword(s):  
Cell Proliferation ◽  
Angiotensin Ii ◽  
Zona Glomerulosa ◽  
Ang Ii ◽  
Adrenal Cell ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Glomerulosa Cells

The effects of angiotensin II (ANG II), the angiotensin type 1 (AT1) receptor antagonist losartan, and low-sodium diet on rat adrenal cell proliferation were studied in vivo with immunocytochemistry. Both ANG II and low-sodium diet increased proliferation of endothelial cells of the zona glomerulosa. Losartan prevented ANG II-induced hyperplasia of glomerulosa cells but not the effects of a low-sodium diet. Glomerulosa cells after ANG II + losartan treatment appeared hypertrophied compared with those of controls. Proliferative effects of ANG II and low-sodium diet in the reticularis were blocked by losartan. No changes were seen in the fasciculata. Proliferation in the medulla was increased with losartan, was decreased by ANG II, but was unaffected by low-sodium diet. In conclusion, 1) cell hypertrophy and proliferation of glomerulosa cells are mediated by AT1 receptor-dependent and -independent processes, 2) proliferation of reticularis cells is controlled by AT1 receptors, and 3) reciprocal control of chromaffin cell proliferation by ANG II may involve indirect AT1-dependent processes.

Obesity augments vasoconstrictor reactivity to angiotensin II in the renal circulation of the Zucker rat

2007 ◽  
Vol 293 (4) ◽  
pp. H2537-H2542 ◽  
Author(s):  
David W. Stepp ◽  
Erika I. Boesen ◽  
Jennifer C. Sullivan ◽  
James D. Mintz ◽  
Clark D. Hair ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Sodium Intake ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Zucker Rats ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Insulin Resistant

Obesity is an emerging risk factor for renal dysfunction, but the mechanisms are poorly understood. Obese patients show heightened renal vasodilation to blockade of the renin-angiotensin system, suggesting deficits in vascular responses to angiotensin II (ANG II). This study tested the hypothesis that obesity augments renal vasoconstriction to ANG II. Lean (LZR), prediabetic obese (OZR), and nonobese fructose-fed Zucker rats (FF-LZR) were studied to determine the effects of obesity and insulin resistance on reactivity of blood pressure and renal blood flow to vasoconstrictors. OZR showed enlargement of the kidneys, elevated urine output, increased sodium intake, and decreased plasma renin activity (PRA) vs. LZR, and renal vasoconstriction to ANG II was augmented in OZR. Renal reactivity to norepinephrine and mesenteric vascular reactivity to ANG II were similar between LZR and OZR. Insulin-resistant FF-LZR had normal reactivity to ANG II, indicating the insulin resistance was an unlikely explanation for the changes observed in OZR. Four weeks on a low-sodium diet (0.08%) to raise PRA reduced reactivity to ANG II in OZR back to normal levels without effect on LZR. From these data, we conclude that in the prediabetic stages of obesity, a decrease in PRA is observed in Zucker rats that may lead to increased renal vascular reactivity to ANG II. This increased reactivity to ANG II may explain the elevated renal vasodilator effects observed in obese humans and provide insight into early changes in renal function that predispose to nephropathy in later stages of the disease.

scholarly journals Angiotensin II-Induced Mitogen-Activated Protein Kinase Phosphatase-1 Expression in Bovine Adrenal Glomerulosa Cells: Implications in Mineralocorticoid Biosynthesis

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5573-5581 ◽  
Author(s):  
Andrés J. Casal ◽  
Stéphane Ryser ◽  
Alessandro M. Capponi ◽  
Carine F. Wang-Buholzer
Keyword(s):  
Angiotensin Ii ◽  
Mapk Pathway ◽  
Fold Increase ◽  
Zona Glomerulosa ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Aldosterone Production ◽  
Glomerulosa Cells

Angiotensin II (AngII) stimulates aldosterone biosynthesis in the zona glomerulosa of the adrenal cortex. AngII also triggers the MAPK pathways (ERK1/2 and p38). Because ERK1/2 phosphorylation is a transient process, phosphatases could play a crucial role in the acute steroidogenic response. Here we show that the dual specificity (threonine/tyrosine) MAPK phosphatase-1 (MKP-1) is present in bovine adrenal glomerulosa cells in primary culture and that AngII markedly increases its expression in a time- and concentration-dependent manner (IC50 = 1 nm), a maximum of 548 ± 10% of controls being reached with 10 nm AngII after 3 h (n = 3, P < 0.01). This effect is completely abolished by losartan, a blocker of the AT1 receptor subtype. Moreover, this AngII-induced MKP-1 expression is reduced to 250 ± 35% of controls (n = 3, P < 0.01) in the presence of U0126, an inhibitor of ERK1/2 phosphorylation, suggesting an involvement of the ERK1/2 MAPK pathway in MKP-1 induction. Indeed, shortly after AngII-induced phosphorylation of ERK1/2 (220% of controls at 30 min), MKP-1 protein expression starts to increase. This increase is associated with a reduction in ERK1/2 phosphorylation, which returns to control values after 3 h of AngII challenge. Enhanced MKP-1 expression is essentially due to a stabilization of MKP-1 mRNA. AngII treatment leads to a 53-fold increase in phosphorylated MKP-1 levels and a doubling of MKP-1 phosphatase activity. Overexpression of MKP-1 results in decreased phosphorylation of ERK1/2 and aldosterone production in response to AngII stimulation. These results strongly suggest that MKP-1 is the specific phosphatase induced by AngII and involved in the negative feedback mechanism ensuring adequate ERK1/2-mediated aldosterone production in response to the hormone.

scholarly journals Sensitization of sodium appetite: evidence for sustained molecular changes in the lamina terminalis

2014 ◽  
Vol 307 (12) ◽  
pp. R1405-R1412 ◽  
Author(s):  
Seth W. Hurley ◽  
Zhongming Zhang ◽  
Terry G. Beltz ◽  
Baojian Xue ◽  
Alan Kim Johnson
Keyword(s):  
Mrna Expression ◽  
Neural Plasticity ◽  
Salt Intake ◽  
Sodium Intake ◽  
Lamina Terminalis ◽  
Mk 801 ◽  
Molecular Alterations ◽  
Sodium Appetite ◽  
History Of ◽  
The Brain

Animals with a history of sodium depletions exhibit increases in salt intake, a phenomenon described as the sensitization of sodium appetite. Using a novel experimental design, the present experiments investigated whether putative molecular markers of neural plasticity and changes in the message for components of the brain renin-angiotensin-aldosterone-system (RAAS) accompany the sensitization of sodium appetite. An initial set of experiments examined whether the glutamatergic N-methyl-d-aspartate receptor antagonist MK-801 would attenuate sodium appetite sensitization and prevent changes in mRNA expression associated with sensitization. Rats with repeated sodium depletions exhibited enhanced sodium appetite and mRNA expression for components of the RAAS in areas along the lamina terminalis (LT), a region of the brain that is important for the regulation of body fluid homeostasis, and these effects were significantly attenuated by MK-801 pretreatment. A second set of experiments investigated whether successive sodium depletions would elevate sodium intake and induce a pattern of fos-B staining consistent with the Δ fos-B isoform in areas along the LT. The pattern of fos-B staining in the subfornical organ was consistent with the characteristics of Δ fos-B expression. Specifically, fos-B/Δ fos-B expression was increased 4 days after the last of a series of sodium depletions, fos-B/Δ fos-B expression was nearly absent in control rats, and the quantity of fos-B/Δ fos-B staining was directly associated with a history of sodium depletions. These findings demonstrate that the sensitization of sodium appetite is associated with sustained molecular alterations in the LT that are indicative of neural plasticity and upregulation of the central RAAS.

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