Abstract 132: Leptin-mediated Aldosterone Secretion Causes Hypertension in Obese Females

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Eric J Belin de Chantemèle ◽  
Miriam Cortez-Cooper ◽  
Joseph Cannon ◽  
Anne-Cécile Huby
Keyword(s):  
Leptin Receptor ◽  
Tyrosine Phosphatase ◽  
Plasma Aldosterone ◽  
Adult Women ◽  
Aldosterone Secretion ◽  
Plasma Angiotensin ◽  
Aldosterone Production ◽  
Β Adrenergic Receptors ◽  
Dose Dependent Increase ◽  
Dose Dependent

Obesity causes hypertension (HTN) in males and females. While leptin contributes to obesity-induced HTN by increasing sympathetic activity, in males, it is unknown whether similar mechanisms trigger HTN in obese females. Females secrete 3 to 4 times more leptin than males, but do not exhibit high sympathetic tone with obesity. They however show inappropriately high aldosterone levels that positively correlate with adiposity and blood pressure (BP). Here we hypothesized that leptin induces HTN by increasing aldosterone production in obese females. Hypersensitivity to leptin, in lean mice deficient in protein tyrosine phosphatase 1B (PTP1B) or high leptin levels, in obese Agouti (Ay/a) mice induced HTN (WT: 115±2; KO: 124±2; a/a: 113±1; Ay/a: 128±7mmHg, p<0.05) but did not increase sympathetic control of BP (response to ganglionic blockade). Leptin sensitization and obesity however elevated plasma aldosterone levels and adrenal aldosterone synthase (CYP11B2) expression, in females. Chronic leptin (KO+AA: 115±5; Ay/a+AA: 114±5mmHg) or mineralocorticoid (KO+spiro:111±5; Ay/a+spiro: 121±6mmHg) receptors inhibition restored BP to baseline levels in females PTP1B KO and obese agouti mice. Leptin or leptin receptor deficiency in female ob/ob and db/db mice, abolished obesity-induced increases in adrenal CYP11B2 and plasma aldosterone while chronic leptin infusion in female mice triggered a dose-dependent increase in adrenal CYP11B2 and plasma aldosterone levels. Leptin-mediated aldosterone secretion was independent of changes in plasma angiotensin II, potassium and corticosterone (index of ACTH levels) and preserved in the presence of losartan or α and β-adrenergic receptors antagonists. Stimulation of human adrenocortical cells with leptin dose-dependently increased CYP11B2 expression and aldosterone production. While investigating the interaction between percentage of body fat, leptin and aldosterone levels in young healthy adult Caucasians we reported a positive correlation between adiposity and aldosterone, and between leptin and aldosterone in adult women only. Together these data suggest that leptin directly regulates aldosterone secretion and that leptin induces HTN via aldosterone dependent mechanisms in obese females.

Selective Hypoaldosteronism: A Study of Steroid Biosynthetic Pathways under Adrenocorticotrophin and Angiotensin II Infusion

1976 ◽  
Vol 51 (s3) ◽  
pp. 335s-337s ◽  
Author(s):  
M. Lebel ◽  
J. H. Grose
Keyword(s):  
Angiotensin Ii ◽  
Zona Glomerulosa ◽  
Plasma Aldosterone ◽  
Zona Fasciculata ◽  
Biosynthetic Pathways ◽  
Normal Functioning ◽  
Probable Consequence ◽  
Plasma Steroids ◽  
Dose Dependent Increase ◽  
Dose Dependent

1. The functional integrity of the adrenal cortex has been tested in a case of selective hypoaldosteronism by adrenocorticotrophin (ACTH) and angiotensin II (AII) infusion. 2. During ACTH infusion a normal functioning zona fasciculata was indicated by the impressive increase of the ACTH-dependent plasma steroids; the aldosterone response was moderate. 3. During AII infusion the plasma aldosterone response was blunted with an unexpected dose-dependent increase in pregnenolone, resulting in abnormal decreasing progesterone/pregnenolone ratios during the infusion, suggesting a slow-down in the conversion of pregnenolone into progesterone. 4. This defect, a probable consequence of chronic renin deficiency on the zona glomerulosa, could be a contributing factor to the hypoaldosteronism.

Detection of Na+ and K+ in the Rat Adrenal Cortex with the Electron Microprobe

1977 ◽  
Vol 53 (5) ◽  
pp. 423-430 ◽  
Author(s):  
C. Decorzant ◽  
A. M. Riondel ◽  
M.-J. Philippe ◽  
J. Bertrand ◽  
M. B. Vallotton
Keyword(s):  
Adrenal Cortex ◽  
Electron Microprobe ◽  
Electrolyte Concentration ◽  
Zona Glomerulosa ◽  
Plasma Aldosterone ◽  
Zona Fasciculata ◽  
Aldosterone Secretion ◽  
Dietary Regimen ◽  
High K ◽  
Aldosterone Production

1. In order to demonstrate whether modification of aldosterone secretion is mediated by parallel changes of K+ in the adrenal zona glomerulosa, the total (intracellular + extracellular) Na+ and K+ content of the rat adrenal cortex was determined with the electron microprobe. 2. Groups of rats were submitted to one of the following dietary regimens: standard, low Na+, high K+ or high Na+. 3. Distribution of Na+ and K+ across the zona glomerulosa and zona fasciculata was compared. Standards of known electrolyte concentration were also analysed. 4. The [Na+] was found to be greater in the zona glomerulosa than in the zona fasciculata but K+ was distributed evenly in both zones. This was independent of dietary regimen. 5. Aldosterone production, assessed by plasma aldosterone concentrations, could not be correlated with zona glomerulosa K+ content.

ALDOSTERONE STIMULATION IN VITRO

1965 ◽  
Vol 48 (2) ◽  
pp. 283-296 ◽  
Author(s):  
Jürg Müller
Keyword(s):  
Adrenal Glands ◽  
High Concentration ◽  
Deficient Diet ◽  
Small Doses ◽  
Aldosterone Production ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Double Isotope ◽  
Very High

ABSTRACT A method is described for assaying aldosterone-stimulating activity in vitro using adrenal glands of rats kept on a sodium deficient diet. The production of aldosterone and corticosterone was measured by double isotope dilution derivative assays. Addition of ACTH or precursor steroids and elevation of the potassium concentration in the incubation medium gave a significant increase of aldosterone production. Angiotensin II showed little aldosterone-stimulating activity and only at a very high concentration. Small doses of a purified extract from human urine lead to a reproducible, significant and dose-dependent increase of aldosterone production without influencing production of corticosterone. The theoretical and practical advantages and limitations of the method are evaluated.

STIMULATION OF ALDOSTERONE BIOSYNTHESIS IN VITRO BY SEROTONIN

1968 ◽  
Vol 59 (1) ◽  
pp. 23-35 ◽  
Author(s):  
Jürg Müller ◽  
Walter H. Ziegler
Keyword(s):  
Fluorescence Spectra ◽  
Retention Volume ◽  
Indole Derivatives ◽  
Rat Serum ◽  
Aldosterone Production ◽  
Other Substances ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Stimulation Of

ABSTRACT The dialysable fraction of rat serum, which was previously shown to stimulate aldosterone production in rat adrenal sections, was chromatographed on Sephadex G-25. Fluorescence spectra indicated that a 5-hydroxyindole derivative was present in the active eluate fraction. The aldosterone-stimulating activity of serum dialysate had a similar retention volume to serotonin and 5-hydroxytryptophan, but was separated from other indole derivatives. Addition of small amounts of pure serotonin to the incubation medium led to a significant and dose-dependent increase of aldosterone and deoxycorticosterone production but did not affect corticosterone production. At higher concentrations, 5-methoxytryptamine, bufotenine and 5-hydroxytryptophan also stimulated aldosterone biosynthesis, whereas a number of other substances chemically or pharmacologically related to serotonin were found to be inactive. Two different serotonin antagonists completely blocked the aldosterone-stimulating effects of serotonin and rat serum but did not influence aldosterone stimulation by ACTH. Serotonin stimulated the incorporation of tritiated cholesterol into aldosterone but not the incorporation of tritiated pregnenolone, indicating that it acts on the conversion of cholesterol to pregnenolone.

Physiological doses of atrial peptide inhibit angiotensin II-stimulated aldosterone secretion

1989 ◽  
Vol 256 (5) ◽  
pp. R1155-R1159
Author(s):  
C. H. Metzler ◽  
D. J. Ramsay
Keyword(s):  
Steady State ◽  
Angiotensin Ii ◽  
Potent Inhibitor ◽  
Plasma Aldosterone ◽  
Electrolyte Balance ◽  
Aldosterone Secretion ◽  
Plasma Aldosterone Concentration ◽  
Physiological Regulator ◽  
Chronically Instrumented Dogs ◽  
Dose Dependent

The current study was designed to investigate the potential of atrial peptide to serve as a physiological regulator of aldosterone secretion. Conscious chronically instrumented dogs were given a constant intravenous infusion of either atrial peptide [ANP-(1-28); 5, 25, or 100 ng.kg-1.min-1] or vehicle (saline). Once steady-state conditions were achieved, angiotensin II was infused in a ramp design to stimulate aldosterone secretion (2.5-40 ng.kg-1.min-1). In the absence of atrial peptide, angiotensin II induced dose-dependent increases in plasma aldosterone concentration. In the presence of a 5-ng.kg-1.min-1 infusion of atrial peptide, the aldosterone response was reduced an average of 65 +/- 11%. When atrial peptide was infused at 25 and 100 ng.kg-1.min-1, the response was totally abolished. These results show that atrial peptide is a potent inhibitor of angiotensin II-stimulated aldosterone secretion. The results suggest that normal variations in plasma atrial peptide concentration can play an important role in the regulation of aldosterone secretion and fluid and electrolyte balance.

Specificity of effect of osmolality on aldosterone secretion

1987 ◽  
Vol 252 (1) ◽  
pp. E118-E123
Author(s):  
R. E. Taylor ◽  
J. T. Glass ◽  
K. J. Radke ◽  
E. G. Schneider
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Glands ◽  
Physical Factor ◽  
Zona Glomerulosa ◽  
Detectable Effect ◽  
Aldosterone Secretion ◽  
Inverse Effect ◽  
Aldosterone Production ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Small (3–7 mM) changes in [NaCl] have a marked inverse effect on angiotensin II- or K-stimulated aldosterone secretion by the isolated, perfused canine adrenal gland. The effect is due to the accompanying changes in osmolality rather than to the changes in [Na] or [Cl]. The present study was undertaken to determine whether osmolality is a specific and discrete signal that modulates the secretion of aldosterone only or is simply a nonspecific physical factor that alters the secretion of other adrenocortical hormones as well. The study also determined whether small changes in osmolality affect the conversion of corticosterone to aldosterone. The secretion of both cortisol and aldosterone by isolated canine adrenal glands responded in a dose-dependent fashion to adrenocorticotropin (ACTH), but in contrast to the rapid and potent modulating action of osmolality reported previously for angiotensin II- or K-stimulated aldosterone secretion, changes in osmolality at the midpoint of ACTH infusion had no detectable effect on either cortisol secretion or, unexpectedly, aldosterone secretion. This indicates that osmolality is a highly specific signal that modulates responsiveness of the zona glomerulosa to the factors, angiotensin II and K, which are considered to be most important in the acute regulation of aldosterone secretion, but does not influence secretion of cortisol by inner zones of the adrenal cortex. In glands treated with agents that block aldosterone production from endogenous precursors, small changes in osmolality had no detectable effect on the conversion of exogenous corticosterone to aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Isoprenaline on the Plasma Concentrations of Angiotensin III in Rats

1979 ◽  
Vol 57 (5) ◽  
pp. 401-407 ◽  
Author(s):  
D. K. Meyer ◽  
M. Eisenreich ◽  
D. Nutto
Keyword(s):  
Angiotensin Ii ◽  
Plasma Concentrations ◽  
Rat Plasma ◽  
Angiotensin Iii ◽  
Plasma Angiotensin ◽  
Exchange Resins ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Dowex 1

1. A new column-chromatographic method is described for the simple and reproducible determination of the concentration of [des-Asp1] angiotensin II (angiotensin III) in rat plasma. 2. The method uses the different abilities of the ion-exchange resins Dowex 1 (X8) and Bio Rex 70 to bind angiotensin II and angiotensin III. Under the conditions used, Bio Rex 70 binds only angiotensin III. Angiotensin II and its hexapeptide metabolite [des-Asp1,des-Arg2]angiotensin II pass the resin with the effluent. Dowex 1 (X8) binds angiotensin II and the hexapeptide metabolite, whereas it does not extract angiotensin III. It does not separate angiotensin II from the hexapeptide. Therefore the sum of both peptides is expressed as angiotensin II-like activity. The ratio of the concentrations, angiotensin II/hexapeptide, was 5:1. 3. In normal rats the plasma concentration of angiotensin III was 20 fmol/ml (sd 15; n = 8), and angiotensin II-like activity was 60 fmol/ml (sd 35; n = 8). 4. The β-sympathomimetic amine isoprenaline caused a time- and dose-dependent increase in plasma angiotensin III and angiotensin II-like activities. 5. Under the conditions studied angiotensin III contributed approximately 25% to the total amount of angiotensins in plasma.

scholarly journals Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism

2017 ◽  
Vol 235 (3) ◽  
pp. 251-265
Author(s):  
Stephan Werth ◽  
Helge Müller-Fielitz ◽  
Walter Raasch
Keyword(s):  
Plasma Aldosterone ◽  
Zucker Rats ◽  
Sprague Dawley ◽  
Aldosterone Secretion ◽  
Sd Rats ◽  
Aldosterone Production ◽  
Sphingosine 1 Phosphate ◽  
H295r Cells ◽  
Obese Zucker Rats

Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100–300 µg/kgbw) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely.

Effects of central and peripheral dopamine antagonism on aldosterone secretion: evidence for adrenal mechanism

1989 ◽  
Vol 257 (4) ◽  
pp. E588-E594
Author(s):  
N. Stern ◽  
P. Eggena ◽  
W. Chandler ◽  
M. L. Tuck
Keyword(s):  
Third Ventricle ◽  
D2 Receptor ◽  
Significant Rise ◽  
Plasma Aldosterone ◽  
Dopamine Antagonist ◽  
Stress Effect ◽  
Central Administration ◽  
Sprague Dawley ◽  
Aldosterone Secretion ◽  
Aldosterone Production

Both domperidone (DOMP) and metoclopramide (MCP) are D2 receptor antagonists, MCP being a central and peripheral dopamine antagonist, whereas DOMP is exclusively a peripheral antagonist. MCP, but not DOMP, has been shown to stimulate aldosterone production. To elucidate whether aldosterone stimulation by dopamine antagonism is centrally mediated, we injected DOMP (28 micrograms/kg body wt) via a cannula into the third ventricle in Sprague-Dawley rats. Plasma aldosterone and renin concentration were measured before and 15 min after the injection. Centrally administered DOMP resulted in an increment in plasma aldosterone (23.8 +/- 7.4 ng/dl) that was not significantly greater than that induced by vehicle alone (15.8 +/- 4.5 ng/dl). This increase was inhibited by pretreatment with dexamethasone (100 micrograms three times daily) and attenuated by captopril (1 mg/kg ip) but not by L-beta-3,4-dihydroxyphenylalanine (30 mg/kg), thus reflecting a stress effect. Similarly, central administration of MCP (21 micrograms/kg) resulted in a significant rise in plasma aldosterone. This increase, however, was eliminated by pretreatment with dexamethasone and attenuated by captopril. Peripherally administered DOMP (280 micrograms/kg) had no effect on plasma aldosterone. The effect of DOMP and MCP on aldosterone secretion by freshly obtained adrenal capsules was also tested. Angiotensin II and MCP, but not DOMP, induced a dose-dependent increase in aldosterone secretion, with a maximal increment (15.7 +/- 5.8 ng.mg capsular protein-1.10 min-1; 50% increase) with MCP at 10(-7) M (P less than 0.01 compared with controls). Dopamine completely inhibited this MCP-induced rise in aldosterone release.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased Expression of u-PA and u-PAR on Monocytes by LDL and Lp(a) Lipoproteins – Consequences for Plasmin Generation and Monocyte Adhesion

1999 ◽  
Vol 81 (04) ◽  
pp. 594-560 ◽  
Author(s):  
Florence Ganné ◽  
Marc Vasse ◽  
Jean-Louis Beaudeu ◽  
Jacqueline Peynet ◽  
Arnaud François ◽  
...  
Keyword(s):  
Fold Increase ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Atheromatous Plaque ◽  
Monocyte Adhesion ◽  
Blood Monocytes ◽  
Proteolytic Cascade ◽  
Ecm Degradation ◽  
Dose Dependent Increase ◽  
Dose Dependent

SummaryMonocyte-derived foam cells figure prominently in rupture-prone regions of atherosclerotic plaque. As urokinase/urokinase-receptor (u-PA/u-PAR) is the trigger of a proteolytic cascade responsible for ECM degradation, we have examined the effect of atherogenic lipoproteins on monocyte surface expression of u-PAR and u-PA. Peripheral blood monocytes, isolated from 10 healthy volunteers, were incubated with 10 to 200 µg/ml of native or oxidised (ox-) atherogenous lipoproteins for 18 h and cell surface expression of u-PA and u-PAR was analysed by flow cytometry. Both LDL and Lp(a) induced a dose-dependent increase in u-PA (1.6-fold increase with 200 μg/ml of ox-LDL) and u-PAR [1.7-fold increase with 200 μg/ml of ox-Lp(a)]. There is a great variability of the response among the donors, some of them remaining non-responders (absence of increase of u-PA or u-PAR) even at 200 μg/ml of lipoproteins. In positive responders, enhanced u-PA/u-PAR is associated with a significant increase of plasmin generation (1.9-fold increase with 200 μg/ml of ox-LDL), as determined by an amidolytic assay. Furthermore, monocyte adhesion to vitronectin and fibrinogen was significantly enhanced by the lipoproteins [respectively 2-fold and 1.7-fold increase with 200 μg/ml of ox-Lp(a)], due to the increase of u-PAR and ICAM-1, which are receptors for vitronectin and fibrinogen. These data suggest that atherogenous lipoproteins could contribute to the development of atheromatous plaque by increasing monocyte adhesion and trigger plaque weakening by inducing ECM degradation.

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