scholarly journals Direct modulation of basal and angiotensin II-stimulated aldosterone secretion by hydrogen ions

2000 ◽  
Vol 166 (1) ◽  
pp. 183-194 ◽  
Author(s):  
RE Kramer ◽  
TV Robinson ◽  
EG Schneider ◽  
TG Smith
Keyword(s):  
Angiotensin Ii ◽  
Free Calcium ◽  
Acid Base Balance ◽  
Aldosterone Secretion ◽  
Plasma Aldosterone Concentration ◽  
Low Concentrations ◽  
Effects Of Ph ◽  
Glomerulosa Cells

Disturbances in acid-base balance in vivo are associated with changes in plasma aldosterone concentration, and in vitro changes in extracellular pH (pH(o)) influence the secretion of aldosterone by adrenocortical tissue or glomerulosa cells. There is considerable disparity, however, as to the direction of the effect. Furthermore, the mechanisms by which pH(o) independently affects aldosterone secretion or interacts with other secretagogues are not defined. Thus, bovine glomerulosa cells maintained in primary monolayer culture were used to examine the direct effects of pH(o) on cytosolic free calcium concentration ([Ca(2+)](i))( )and aldosterone secretion under basal and angiotensin II (AngII)-stimulated conditions. pH(o) was varied from 7.0 to 7.8 (corresponding inversely to changes in extracellular H(+) concentration from 16 nM to 100 nM). Whereas an elevation of pH(o) from 7.4 to 7.8 had no consistent effect, reductions of pH(o) from 7.4 to 7.2 or 7.0 caused proportionate increases in aldosterone secretion that were accompanied by increases in transmembrane Ca(2+) fluxes and [Ca(2+)](i). These effects were abolished by removal of extracellular Ca(2+). A decrease in pH(o) from 7.4 to 7.0 also enhanced AngII-stimulated aldosterone secretion. This effect was more pronounced at low concentrations of AngII and was manifested as an increase in the magnitude of the secretory response with no effect on potency. In contrast to its effect on AngII-stimulated aldosterone secretion, a reduction of pH(o) from 7.4 to 7.0 inhibited the Ca(2+) signal elicited by low concentrations (</=1x10(-10) M) of AngII, but did not affect the increase in [Ca(2+)](i) caused by a maximal concentration (1x10(-8) M) of AngII. These data suggest that pH(o) (i.e. H(+)) has multiple effects on aldosterone secretion. It independently increases aldosterone secretion through a mechanism involving Ca(2+) influx and an increase in [Ca(2+)](i). Also, it modulates the action of AngII by both decreasing the magnitude of the AngII-stimulated Ca(2+) signal and increasing the sensitivity of a more distal site to intracellular Ca(2+). The latter action appears to be a more important determinant in the effects of pH(o) on AngII-stimulated aldosterone secretion.

Effects of angiotensin II, ACTH, and KCl on the adrenal renin-angiotensin system in the rat

1990 ◽  
Vol 122 (3) ◽  
pp. 369-373 ◽  
Author(s):  
Hiroyuki Sasamura ◽  
Hiromichi Suzuki ◽  
Ryuichi Kato ◽  
Takao Saruta
Keyword(s):  
Angiotensin Ii ◽  
Statistical Significance ◽  
Renin Angiotensin System ◽  
Plasma Aldosterone ◽  
Aldosterone Secretion ◽  
Plasma Aldosterone Concentration ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Captopril Treatment

Abstract Angiotensin II, ACTH and potassium chloride were administered to rats for 6 days and the effects on adrenal renin-like activity and adrenal angiotensin II/III immunoreactivity were investigated. Rats infused with angiotensin II(140 pmol/min) either ip or sc showed increases in adrenal angiotensin II/III immunoreactivity (p<0.05) and plasma aldosterone concentration (p<0.05), but no change in adrenal renin-like activity. Captopril treatment of angiotensin Il-infused rats caused a slight decrease in angiotensin II/III immunoreactivity which did not reach statistical significance. In contrast, rats treated with ACTH (Cortrosyn-Z, 3 IU/day, sc) showed an increase in adrenal renin-like activity (p<0.01), but no significant change in adrenal angiotensin II/III immunoreactivity. Rats treated with KCl in drinking water showed increases (p<0.05) in adrenal renin-like activity, adrenal angiotensin II/III immunoreactivity, and plasma aldosterone. These results suggest that angiotensin II, ACTH and potassium, three major regulators of aldosterone secretion by the adrenal gland, have different effects on the adrenal renin-angiotensin system when administered in vivo.

Low oxygen selectively inhibits aldosterone secretion from bovine adrenocortical cells in vitro

1989 ◽  
Vol 256 (5) ◽  
pp. E640-E644 ◽  
Author(s):  
H. Raff ◽  
D. L. Ball ◽  
T. L. Goodfriend
Keyword(s):  
Angiotensin Ii ◽  
Adrenocorticotropic Hormone ◽  
Dibutyryl Camp ◽  
Low Oxygen ◽  
Aldosterone Secretion ◽  
Adrenocortical Cells ◽  
Systemic Hypoxia ◽  
Tissue Po2

Systemic hypoxia has been reported to inhibit selectively aldosterone secretion in vivo. The mechanism of this inhibition has not been elucidated. We hypothesized that decreased tissue PO2 directly inhibited aldosteronogenesis. To test this hypothesis, we exposed dispersed adrenocortical cells (90% glomerulosa/10% fasciculata) to decreased PO2 in vitro while simultaneously stimulating aldosterone secretion with angiotensin II, N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (dibutyryl cAMP) adrenocorticotropic hormone (ACTH)-(1-24), or progesterone. Decreasing buffer PO2 from approximately 150 to approximately 85 Torr significantly inhibited basal and angiotensin II, cAMP, progesterone, and ACTH-stimulated aldosterone secretion at all doses of secretagogue. Inhibition was largest for angiotensin II (55 +/- 9% inhibition at 1 microM) and cAMP (54 +/- 8% at 3 mM) and lowest for ACTH (24% at 100 nM) and basal aldosterone secretion (31 +/- 7%). This inhibition was reversed by returning the buffer PO2 to 150 Torr. Cortisol secretion was not significantly inhibited by decreased buffer PO2. We conclude that decreased buffer PO2 significantly inhibits aldosterone secretion in vitro, and this inhibition is reversible and specific. Hypoxia-induced inhibition of aldosterone secretion in vivo may be caused, at least in part, by a direct effect of low tissue PO2 within the adrenal cortex.

Control of zona glomerulosa function in the isolated perfused rat adrenal gland in situ

1985 ◽  
Vol 104 (3) ◽  
pp. 387-395 ◽  
Author(s):  
J. P. Hinson ◽  
G. P. Vinson ◽  
B. J. Whitehouse ◽  
G. Price
Keyword(s):  
Angiotensin Ii ◽  
Zona Glomerulosa ◽  
Adrenocortical Function ◽  
Specific Marker ◽  
Dependent Manner ◽  
Aldosterone Secretion ◽  
In Vitro Techniques ◽  
Corticosterone Secretion

ABSTRACT The extent to which results obtained using in-vitro techniques can be taken to reflect in-vivo physiological responses in the study of adrenocortical function has not been subjected to systematic study. Some evidence suggests that in-vitro preparative methods may affect the secreted steroid profile. For this reason it seemed desirable to study adrenal function using an isolated perfused whole gland technique, and this study reports results obtained with known aldosterone stimulants. Angiotensin II, ACTH and potassium ions all stimulated aldosterone secretion in a dose-dependent manner. The stimulation thresholds of these substances were compatible with their normal circulating concentrations. For angiotensin II stimulation this preparation was two orders of magnitude more sensitive than any in-vitro preparation. Most importantly, the specific glomerulosa effectors, angiotensin II and potassium, selectively stimulated aldosterone output, and had no consistent effect on corticosterone secretion at any dose used. On the other hand, ACTH stimulated both corticosterone and aldosterone output at all effective concentrations. The actions of α-MSH were also studied using this preparation. Low doses of α-MSH selectively stimulated aldosterone secretion, while higher doses were needed to stimulate corticosterone. The onset of response to all stimulants was invariably seen within the first 10 min after administration of stimulants. Maximal aldosterone output was achieved within the first 10 min whereas corticosterone secretion usually peaked 10–20 min later. The amount of aldosterone produced by this preparation was much higher than the amount produced by dispersed cell preparations, and closely approximated to the levels of aldosterone obtained in adrenal vein blood. The data indicate that the isolated circulation perfused gland system is a sensitive preparation which approximates to the physiological condition. In particular, aldosterone is the prominent glomerulosa product, and corticosterone is, in this system, a more specific marker for inner zone function. J. Endocr. (1985) 104, 387–395

Effects of heparin treatments in vivo and in vitro on adrenal angiotensin II receptors and angiotensin II-induced aldosterone production in rats

1988 ◽  
Vol 119 (3) ◽  
pp. 367-372 ◽  
Author(s):  
Sadahide Azukizawa ◽  
Ikuyo Iwasaki ◽  
Toshikazu Kigoshi ◽  
Kenzo Uchida ◽  
Shinpei Morimoto
Keyword(s):  
Angiotensin Ii ◽  
Benzyl Alcohol ◽  
Specific Binding ◽  
Angiotensin Ii Receptors ◽  
Scatchard Analysis ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Heparin Preparation

Abstract. To evaluate the heparin effects in vivo and in vitro on adrenal angiotensin II receptors and angiotensin II-induced aldosterone production, we examined the angiotensin II binding and the maximum angiotensin II-induced aldosterone production using adrenal glomerulosa cells from rats treated with a heparin preparation containing benzyl alcohol (1500 IU/kg, twice daily for 6 weeks) or cells to which heparin (300 IU/l) was directly added. Comparison was made using the cells from rats treated with vehicle or the cells to which vehicle was directly added. Specific binding of [125I]iodo-angiotensin II was decreased in the cells from heparin-treated rats or in the heparin-treated cells. Scatchard analysis showed that the decrease in binding was due to a decrease in both the number and the affinity of angiotensin II receptors in the cells from heparin-treated rats and a decrease in the number, but not the affinity, of the receptors in the heparin-treated cells. Heparin also caused a decrease in the maximum angiotensin Il-induced production, but not the basal production, of aldosterone in the cells from heparin-treated rats and in the heparin-treated cells. These data suggest that heparin interacts with adrenal angiotensin II receptors to inhibit the angiotensin Il-induced aldosterone production.

Long-term survival and aldosterone secretion pattern of aldosteronoma in culture

1983 ◽  
Vol 104 (4) ◽  
pp. 495-501 ◽  
Author(s):  
Tetsuro Okabe ◽  
Hiroshi Hidaka ◽  
Nakaaki Ohsawa ◽  
Toshio Tsushima
Keyword(s):  
Angiotensin Ii ◽  
Primary Aldosteronism ◽  
Culture Medium ◽  
Cultured Cells ◽  
Aldosterone Secretion ◽  
Term Survival ◽  
Eosinophilic Cytoplasm

Abstract. In an attempt to obtain an in vitro experimental model for aldosteronoma, primary culture was initiated with adenomas from 3 patients with primary aldosteronism. The cells grown in culture retained the morphology and functional properties characteristic of aldosteronoma cells well for periods of up to 200 days. The cells formed monolayer cell colonies and showed an epithelioid morphology with small nuclei containing prominent nucleoli. The cells possessed a clear, eosinophilic cytoplasm resembling that of aldosteronoma cells in vivo. The cultured cells continued to secrete large amounts of aldosterone throughout the culture period. The cells responded to angiotensin II and III by increased release of aldosterone into the culture medium. They also responded to Db-cAMP and ACTH by increased secretion of the hormone.

scholarly journals Effect of High Extracellular Phosphate Concentration on Arachidonic Acid Production by Parathyroid TissueIn Vitro

2000 ◽  
Vol 11 (9) ◽  
pp. 1712-1718 ◽  
Author(s):  
YOLANDA ALMADÉN ◽  
ANTONIO CANALEJO ◽  
EVARISTO BALLESTEROS ◽  
GRACIA AÑÓN ◽  
MARIANO RODRÍGUEZ
Keyword(s):  
Arachidonic Acid ◽  
Angiotensin Ii ◽  
Intracellular Signaling ◽  
Parathyroid Tissue ◽  
Phosphate Concentration ◽  
High Calcium ◽  
Glomerulosa Cells ◽  
High Phosphate

Abstract.Recentin vivoandin vitrostudies show that high phosphate directly stimulates parathyroid hormone (PTH) secretion. However, little is known about the intracellular signaling system involved in the regulation of PTH secretion by extracellular phosphate. High extracellular calcium is coupled to the activation of phospholipase A2(PLA2) and the formation of arachidonic acid (AA), a potent inhibitor of PTH release. The present study was designed to evaluate whether a high phosphate concentration has an effect on the PLA2-AA pathway in parathyroid cells.In vitroexperiments were performed in parathyroid tissue obtained from normal rats and dogs. AA production was measured in parathyroid tissue in response to 1- and 4-mM phosphate concentration and after addition of PLA2to the medium. To determine whether the effect of phosphate on AA production in parathyroid cells was tissue specific, separate experiments were performed to test the effect of phosphate in rat adrenal glomerulosa cells, which are known to increase AA production in response to angiotensin II. The effect of sulfate, an ion with chemical characteristics similar to phosphate, on PTH secretion was also evaluated. In parathyroid tissue, a high phosphate concentration decreased the high calcium-induced AA production. This effect of phosphate was associated with an increase in PTH secretion. The addition of AA reversed the stimulatory effect of phosphate on PTH secretion. In another type of AA-responsive tissue, the adrenal glomerulosa, a high phosphate concentration did not affect the production of AA when stimulated by angiotensin II. In a normal phosphate concentration, the addition of PLA2stimulated AA production and decreased the PTH secretion. However, in a 4-mM phosphate concentration, the addition of PLA2did not reduce PTH secretion and did not stimulate AA production. Finally, sulfate did not affect PTH secretion. In conclusion, a high phosphate concentration affects the production of AA by parathyroid tissue. This effect of phosphate may be the mechanism by which a high phosphate concentration stimulates PTH secretion.

Rat adrenal cell sensitivity to angiotensin II, alpha-1-24-ACTH, and potassium: a comparative study.

1977 ◽  
Vol 233 (5) ◽  
pp. E402
Author(s):  
L M Braley ◽  
G H Williams
Keyword(s):  
Angiotensin Ii ◽  
Comparative Study ◽  
Maximum Response ◽  
Aldosterone Secretion ◽  
Cell Sensitivity ◽  
Adrenal Cell ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Small Increments

Rat adrenal glomerulosa and fasciculata-reticularis cell sensitivity to comparable molar doses of angiotensin II (AII) (2.4 X 10(-12) to 2.4 X 10(-4) M) and ACTH (alpha-1-24-adrenocorticotropin) (3.5 X 10(-13) to 3.5 X 10(-8) M) as well as small increments in potassium (K+) (3.7 to 13 meq/liter) was investigated. Glomerulose cells responded to physiological levels of AII (2.4 X 10(-10) M) and alpha-1-24-ACTH (3.5 X 10(-12) M), whereas an increment of as little 0.3 meq/liter in medium K+ also significantly increased aldosterone production. Of the three stimuli, alpha-1-24-ACTH caused the greatest aldosterone rise (11 times control). Fasciculata-reticularis cells responded only to alpha-1-24-ACTH. Whereas the threshold sensitivity was no lower than with glomerulosa cells, the maximum response was significantly greater (63 times control). These findings are consistent with findings documented in vivo in man, suggesting that the control of aldosterone secretion is similar in these two species.

scholarly journals Angiotensin III Stimulates Aldosterone Secretion from Adrenal Gland Partially via Angiotensin II Type 2 Receptor But Not Angiotensin II Type 1 Receptor

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1582-1588 ◽  
Author(s):  
Junichi Yatabe ◽  
Minoru Yoneda ◽  
Midori S. Yatabe ◽  
Tsuyoshi Watanabe ◽  
Robin A. Felder ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Aldosterone Secretion ◽  
Plasma Aldosterone Concentration ◽  
Ang Iv

Abstract Angiotensin II (Ang II) and Ang III stimulate aldosterone secretion by adrenal glomerulosa, but the angiotensin receptor subtypes involved and the effects of Ang IV and Ang (1–7) are not clear. In vitro, different angiotensins were added to rat adrenal glomerulosa, and aldosterone concentration in the medium was measured. Ang II-induced aldosterone release was blocked (30.3 ± 7.1%) by an Ang II type 2 receptor (AT2R) antagonist, PD123319. Candesartan, an Ang II type 1 receptor (AT1R) antagonist, also blocked Ang II-induced aldosterone release (42.9 ± 4.8%). Coadministration of candesartan and PD123319 almost abolished the Ang II-induced aldosterone release. A selective AT2R agonist, CGP42112, was used to confirm the effects of AT2R. CGP42112 increased aldosterone secretion, which was almost completely inhibited by PD123319. In addition to Ang II, Ang III also induced aldosterone release, which was not blocked by candesartan. However, PD123319 blocked 22.4 ± 10.5% of the Ang III-induced aldosterone secretion. Ang IV and Ang (1–7) did not induce adrenal aldosterone secretion. In vivo, both Ang II and Ang III infusion increased plasma aldosterone concentration, but only Ang II elevated blood pressure. Ang IV and Ang (1–7) infusion did not affect blood pressure or aldosterone concentration. In conclusion, this report showed for the first time that AT2R partially mediates Ang III-induced aldosterone release, but not AT1R. Also, over 60% of Ang III-induced aldosterone release may be independent of both AT1R and AT2R. Ang III and AT2R signaling may have a role in the pathophysiology of aldosterone breakthrough.

Effect of pH and inhibitors on beta-amyloid fibril assembly

1996 ◽  
Vol 54 ◽  
pp. 752-753
Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Peptide Fragment ◽  
Hydrophobic Peptides ◽  
Amyloid Fibril Formation ◽  
Effects Of Ph ◽  
Severity Of The Disease ◽  
Kinetics Of ◽  
The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

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