Effect of angiotensin II and deoxycorticosterone infusion on vascular angiotensin II receptors in rats

1984 ◽  
Vol 246 (4) ◽  
pp. H608-H614 ◽  
Author(s):  
E. L. Schiffrin ◽  
J. Gutkowska ◽  
J. Genest
Keyword(s):  
Angiotensin Ii ◽  
Binding Sites ◽  
Binding Capacity ◽  
Plasma Renin ◽  
Intravenous Dose ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Plasma Aldosterone Concentration ◽  
Dose Dependent Fashion ◽  
Dose Dependent

The effect of angiotensin II (ANG II) and deoxycorticosterone acetate (DOCA) on the density (Bmax) and affinity (Kd) of binding sites for 125I-ANG II was investigated in a particulate fraction prepared from rat mesenteric arteriolar arcades. Rats were infused with ANG II via Alzet osmotic minipumps at a dose of 200 ng X kg-1 X min-1 intraperitoneally or 60 and 200 ng X kg-1 X min-1 intravenously for 5 days. Bmax was 127 +/- 5 fmol/mg protein, and Kd was 0.8 +/- 0.1 nM in controls and was reduced significantly after the intraperitoneal infusion (111 +/- 10 fmol/mg) or the lower intravenous dose (111 +/- 9 fmol/mg), whereas after the higher intravenous dose Bmax did not change (144 +/- 14 fmol/mg). Kd was unaffected in all groups. Plasma renin activity (PRA) was reduced, and plasma ANG II increased in a dose-dependent fashion after ANG II infusion. Plasma aldosterone concentration increased only in the group infused with ANG II at 200 ng X kg-1 X min-1 intravenously (to 33.8 +/- 8.0 ng/dl from 11.6 +/- 3.4). In rats implanted subcutaneously with silicone rubber impregnated with DOCA, Bmax for 125I-ANG II was significantly increased (to 142 +/- 4 fmol/mg), whereas rats receiving 1% NaCl in their drinking water had no change in binding capacity, although PRA was lower in both groups. DOCA infusion, when combined with the intravenous dose of ANG II that reduced Bmax, antagonized this action of ANG II. DOCA infusion into sodium-depleted rats partially corrected the down-regulation of vascular ANG II receptors independent of changes in PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Renin, Angiotensin and Aldosterone in Human Pregnancy and the Menstrual Cycle

1971 ◽  
Vol 16 (3) ◽  
pp. 183-196 ◽  
Author(s):  
J. I. S. Robertson ◽  
R. J. Weir ◽  
G. O. Düsterdieck ◽  
R. Fraser ◽  
M. Tree
Keyword(s):  
Angiotensin Ii ◽  
Plasma Renin ◽  
Normal Pregnancy ◽  
Maternal Plasma ◽  
Plasma Aldosterone ◽  
Sodium Depletion ◽  
Aldosterone Secretion ◽  
Renin Substrate ◽  
Plasma Aldosterone Concentration ◽  
In Pregnancy

Aldosterone secretion is frequently, although not invariably, increased above the normal non-pregnant range in normal pregnancy. Substantial increases in plasma aldosterone concentration have also been demonstrated as early as the sixteenth week. In pregnancy, aldosterone secretion rate responds in the usual way to changes in sodium intake. Plasma renin concentration is frequently, but not invariably, raised above the normal non-pregnant range. Plasma renin-substrate is consistently raised in pregnancy. Plasma angiotensin II has also been shown usually to be raised in a series of pregnant women. A significant positive correlation has been shown between the maternal plasma aldosterone concentration and the product of the concurrent plasma renin and renin-substrate concentrations. This suggests that the increased plasma aldosterone in pregnancy is the consequence of an increase in circulating angiotensin II, which in turn is related to the level of both renin and its substrate in maternal blood. For these reasons, estimations of renin activity in pregnancy are of dubious value. The increased renin, angiotensin and aldosterone concentrations may represent a tendency to maternal sodium depletion, probably mainly a consequence of the increased glomerular filtration rate. It is possible that the nausea and other symptoms of early pregnancy may be a consequence of this tendency to sodium depletion, with its attendant hormonal changes. In ‘pre-eclampsia’, renin and aldosterone values are generally slightly lower than in normal pregnancy. Human chorion can apparently synthesize renin independently of the kidney. The physiological significance of this remains at present obscure, but it seems unlikely that this source contributes much, if at all, to the often elevated maternal plasma renin. Plasma renin, renin-activity and angiotensin II concentrations, and aldosterone secretion are increased in the luteal phase of the menstrual cycle.

Inhibition of angiotensinogen production by angiotensin II analogues in human hepatoma cell line

1989 ◽  
Vol 257 (5) ◽  
pp. C888-C895 ◽  
Author(s):  
E. Coezy ◽  
I. Darby ◽  
J. Mizrahi ◽  
B. Cantau ◽  
M. H. Donnadieu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cell Line ◽  
Binding Sites ◽  
Inhibitory Effect ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Human Hepatoma ◽  
Ang Ii ◽  
Hep G2 ◽  
Dose Dependent

The aim of this study was to examine in Hep G2, a human hepatoma-derived cell line, the presence of angiotensin II (ANG II) receptors and the effect of ANG II and its analogues on angiotensinogen production. The presence of ANG II receptors was demonstrated using a long-acting ANG II analogue, 125I-labeled [Sar1]ANG II. A single class of specific binding sites was identified in these cells with a dissociation constant (Kd) of 2 nM. The number and affinity of these binding sites were not changed by [Sar1]ANG II treatment over 24 h. ANG II showed an inhibitory effect on angiotensinogen production. [Sar1]ANG II also exhibited a similar inhibitory effect as that of ANG II but to a greater extent and therefore was used throughout these studies. [Sar1]ANG II inhibited angiotensinogen production in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) of 2 nM. Other ANG II analogues showed similar effects on angiotensinogen production. In order of decreasing ability, they were [Sar1]ANG II greater than [Sar1-Ala8]ANG II greater than [Sar1-Val8]ANG II greater than [Sar1-Val5-(Br5)-Phe8]ANG II greater than [Sar1-Val5-DPhe8]ANG II. Results of these studies show that the Hep G2 cell possesses specific ANG II receptors and that [Sar1]ANG II induces a dose-dependent inhibition of angiotensinogen production in this system.

Central effects of angiotensin II and dopamine in sodium-depleted sheep

1985 ◽  
Vol 248 (5) ◽  
pp. R541-R548
Author(s):  
B. S. Huang ◽  
R. L. Malvin ◽  
R. J. Grekin
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Angiotensin System ◽  
Aldosterone Level ◽  
Central Effects ◽  
Dopaminergic Pathway

The effects of intracerebroventricular (IVT) infusion of angiotensin II (ANG II), the converting enzyme inhibitor SQ 20881, and dopamine were studied in 15 conscious Na-depleted sheep. IVT ANG II (25 ng/min) significantly increased plasma aldosterone (163 +/- 24%) and vasopressin (ADH) (533 +/- 100%). Plasma renin activity (PRA) was decreased to 64 +/- 10% of basal. IVT SQ (1 microgram/min) decreased aldosterone to 70 +/- 10% and ADH to 55 +/- 9% of basal. PRA increased to 124 +/- 10%. There were no significant changes in plasma Na, K, or cortisol levels nor in mean arterial or intracranial pressure after either infusion. Increasing the dose of SQ to 10 micrograms/min resulted in an increased magnitude of change in the same variables. IVT SQ (1 microgram/min) significantly decreased aldosterone level in five nephrectomized sheep. The responses to IVT dopamine (20 micrograms/min) were qualitatively similar to those elicited by IVT SQ. These data support the existence of an endogenous brain renin-angiotensin system (RAS) independent of the renal RAS. ANG II acts centrally to regulate plasma ADH, aldosterone, and PRA levels. The similarity of the responses to SQ and dopamine suggests that a dopaminergic pathway may be involved in these responses.

scholarly journals Effects of Ramipril on the Aldosterone/Renin Ratio and the Aldosterone/Angiotensin II Ratio in Patients With Primary Aldosteronism

Hypertension ◽  
2020 ◽  
Vol 76 (2) ◽  
pp. 488-496 ◽  
Author(s):  
Zeng Guo ◽  
Marko Poglitsch ◽  
Diane Cowley ◽  
Oliver Domenig ◽  
Brett C. McWhinney ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Ace Inhibitors ◽  
Primary Aldosteronism ◽  
Characteristic Curve ◽  
False Negative ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Renin Activity ◽  
Plasma Aldosterone Concentration

The aldosterone/renin ratio (ARR) is currently considered the most reliable approach for case detection of primary aldosteronism (PA). ACE (Angiotensin-converting enzyme) inhibitors are known to raise renin and lower aldosterone levels, thereby causing false-negative ARR results. Because ACE inhibitors lower angiotensin II levels, we hypothesized that the aldosterone/equilibrium angiotensin II (eqAngII) ratio (AA2R) would remain elevated in PA. Receiver operating characteristic curve analysis involving 60 patients with PA and 40 patients without PA revealed that the AA2R was not inferior to the ARR in screening for PA. When using liquid chromatography-tandem mass spectrometry to measure plasma aldosterone concentration, the predicted optimal AA2R cutoff for PA screening was 8.3 (pmol/L)/(pmol/L). We then compared the diagnostic performance of the AA2R with the ARR among 25 patients with PA administered ramipril (5 mg/day) for 2 weeks. Compared with basally, plasma levels of equilibrium angiotensin I (eqAngI) and direct renin concentration increased significantly ( P <0.01 or P <0.05) after ramipril treatment, whereas eqAngII and ACE activity (eqAngII/eqAngI) decreased significantly ( P <0.01). The changes of plasma renin activity and plasma aldosterone concentration in the current study were not significant. On day 14, 4 patients displayed false-negative results using ARR_direct renin concentration (plasma aldosterone concentration/direct renin concentration), 3 of whom also showed false-negative ARR_plasma renin activity (plasma aldosterone concentration/plasma renin activity). On day 15, 2 patients still demonstrated false-negative ARR_plasma renin activity, one of whom also showed a false-negative ARR_direct renin concentration. No false-negative AA2R results were observed on either day 14 or 15. In conclusion, compared with ARR which can be affected by ACE inhibitors causing false-negative screening results, the AA2R seems to be superior in detecting PA among subjects receiving ACE inhibitors.

Agonist-induced internalisation of the angiotensin II-binding sites from plasma membranes of isolated rat hepatocytes

1997 ◽  
Vol 152 (3) ◽  
pp. 407-412 ◽  
Author(s):  
M Montiel ◽  
M C Caro ◽  
E Jiménez
Keyword(s):  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Binding Sites ◽  
Plasma Membranes ◽  
Binding Capacity ◽  
Rat Hepatocytes ◽  
Receptor Complex ◽  
Ang Ii ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

Angiotensin II (Ang II) provokes rapid internalisation of its receptor from plasma membranes in isolated rat hepatocytes. After 10 min stimulation with Ang II, plasma membrane lost about 60% of its 125I-Ang II-binding capacity. Internalisation was blocked by phenylarsine oxide (PhAsO), whereas okadaic acid, which markedly reduced the sustained phase of calcium mobilization, did not have a preventive effect on Ang II–receptor complex sequestration. These data suggest that Ang II receptor internalisation is probably independent of a phosphorylation/dephosphorylation cycle of critical serine/threonine residues in the receptor molecule. To establish a relationship between sequestration of the Ang II receptor and the physical properties of the Ang II-binding sites, 125I-Ang II–receptor complex profiles were analysed by isoelectric focusing. In plasma membrane preparations two predominant Ang II-binding sites, migrating to pI 6·8 and 6·5 were found. After exposure to Ang II, cells lost 125I-Ang II-binding capacity to the Ang II–receptor complex migrating at pI 6·8 which was prevented in PhAsO-treated cells. Pretreatment of hepatocytes with okadaic acid did not modify Ang II–receptor complex profiles, indicating that the binding sites corresponding to pI 6·5 and pI 6·8 do not represent a phosphorylated and/or non-phosphorylated form of the Ang II receptor. The results show that the Ang II–receptor complex isoform at pI 6·8 represents a functional form of the type-1 Ang II receptor. Further studies are necessary to identify the Ang II-related nature of the binding sites corresponding to pI 6·5. Journal of Endocrinology (1997) 152, 407–412

A new transgenic rat model overexpressing the angiotensin II type 2 receptor provides evidence for inhibition of cell proliferation in the outer adrenal cortex

2012 ◽  
Vol 302 (9) ◽  
pp. E1044-E1054 ◽  
Author(s):  
Barbara Peters ◽  
Dirk Podlich ◽  
Michael Ritter ◽  
Anja Müller ◽  
Heike Wanka ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Angiotensin Ii ◽  
Binding Sites ◽  
Plasma Aldosterone ◽  
Transgenic Rat ◽  
Moderate Increase ◽  
Ang Ii ◽  
Ki 67 ◽  
Plasma Urea ◽  
Aldosterone Production

This study aimed to elucidate the role of the AT2 receptor (AT2R), which is expressed and upregulated in the adrenal zona glomerulosa (ZG) under conditions of increased aldosterone production. We developed a novel transgenic rat (TGR; TGRCXmAT2R) that overexpresses the AT2R in the adrenal gland, heart, kidney, brain, skeletal muscle, testes, lung, spleen, aorta, and vein. As a consequence the total angiotensin II (Ang II) binding sites increased 7.8-fold in the kidney, 25-fold in the heart, and twofold in the adrenals. The AT2R number amounted to 82–98% of total Ang II binding sites. In the ZG of TGRCXmAT2R, the AT2R density was elevated threefold relative to wild-type (WT) littermates, whereas AT1R density remained unchanged. TGRCXmAT2R rats were viable and exhibited normal reproduction, blood pressure, and kidney function. Notably, a slightly but significantly reduced body weight and a moderate increase in plasma urea were observed. With respect to adrenal function, 24-h urinary and plasma aldosterone concentrations were unaffected in TGRCXmAT2R at baseline. Three and 14 days of Ang II infusion (300 ng·min−1·kg−1) increased plasma aldosterone levels in WT and in TGR. These changes were completely abolished by the AT1R blocker losartan. Of note, glomerulosa cell proliferation, as indicated by the number of Ki-67-positive glomerulosa cells, was stimulated by Ang II in TGR and WT rats; however, this increase was significantly attenuated in TGR overexpressing the AT2R. In conclusion, AT2R in the adrenal ZG inhibits Ang II-induced cell proliferation but has no obvious lasting effect on the regulation of the aldosterone production at the investigated stages.

Dietary protein increases plasma renin and reduces pressor reactivity to angiotensin II

1986 ◽  
Vol 251 (1) ◽  
pp. F34-F39 ◽  
Author(s):  
M. S. Paller ◽  
T. H. Hostetter
Keyword(s):  
Angiotensin Ii ◽  
Dietary Protein ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Chronic Administration ◽  
Plasma Renin ◽  
Prostaglandin Synthesis ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Inhibition Of Prostaglandin Synthesis

The effect of dietary protein on the renin-angiotensin system was studied in rats. Rats were fed isocaloric, 50% (high protein, HP), or 6% (low protein, LP) protein diets with identical electrolyte content for 10 days. Food intake and electrolyte excretion were equivalent on the two diets. Plasma renin activity (PRA) was higher in HP (10.0 +/- 2.5 vs. 3.5 +/- 0.5 ng ANG I . ml-1 . h-1, P less than 0.02) as was plasma aldosterone. However, in conscious rats mean arterial pressure (MAP) was not different between groups. The pressor response to graded doses of angiotensin II (ANG II) was diminished by 30-60% with HP (all doses, P less than 0.05). ANG II binding by mesenteric artery smooth muscle particles did not differ between HP and LP. Chronic administration of captopril did not normalize the pressor response in HP. Urinary prostaglandin (PG) E and 6-keto-PGF1 alpha excretion was markedly increased by the HP diet. Acute inhibition of prostaglandin synthesis with meclofenamate restored the pressor response to ANG II in HP to that in LP. In summary, a HP diet increased PRA, plasma aldosterone, urinary PGE, and 6-keto-PGF1 alpha and decreased pressor responsiveness to ANG II. Resistance to ANG II was not reversed by chronic converting enzyme inhibition but was abolished by inhibition of prostaglandin synthesis.

Salt sensitivity in hypertensive rats with angiotensin II administration

1990 ◽  
Vol 259 (5) ◽  
pp. R1012-R1016 ◽  
Author(s):  
K. Ando ◽  
Y. Sato ◽  
T. Fujita
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Salt Sensitivity ◽  
Ang Ii ◽  
Short Term ◽  
Salt Loading ◽  
Salt Diet ◽  
Dose Dependent Fashion ◽  
Dose Dependent

We examined the salt sensitivity of blood pressure in angiotensin II (ANG II)-induced hypertension. Wistar rats, salt loaded (0.66, 2, or 8% salt-containing diet) for 4 or 12 days, were infused intravenously with 15 or 60 ng/min of ANG II. Systolic blood pressure (SBP) was not increased by long-term (12 days) salt loading, and SBP was unchanged with ANG II and normal-salt (0.66%) diet. However, when combined with salt loading, ANG II produced hypertension in a dose-dependent fashion; compared with control (120 +/- 2 mmHg), SBP was increased with 15 ng/min of ANG II and 8% salt diet (145 +/- 5 mmHg, P less than 0.05) and with 60 ng/min of ANG II and either 2 or 8% salt diet (149 +/- 8 and 174 +/- 8 mmHg, P less than 0.05, respectively). Na space (exchangeable Na) was increased in a roughly similar pattern and correlated significantly (r = 0.531, P less than 0.05) with SBP. However, with 15 ng/min of ANG II, Na space was not different among rats on either level of salt loading, although the 8% salt diet elevated SBP. Data obtained with short-term (4 days) treatment indicate that an elevated Na space preceded development of hypertension. With 15 ng/min of ANG II and 8% salt diet for 4 days, Na space was markedly (P less than 0.05) increased, but SBP was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

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