scholarly journals Liver Steatosis is a Component of the Hepatocardiorenal Syndrome Provoked by a High-Lipid Diet and Activation of Ang II Pathways in Rats

2021 ◽  
Author(s):  
Thuany Crisóstomo ◽  
Marco A. E. Pardal ◽  
Simone A. Herdy ◽  
Humberto Muzi-Filho ◽  
Debora B. Mello ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Liver Steatosis ◽  
Chronic Administration ◽  
Ang Ii ◽  
High Lipid ◽  
High Lipid Diet ◽  
Lipid Diet

Overweight/obesity is a growing pandemic nowadays that affects many organs and tissues. We have investigated whether a high-lipid diet provokes an imbalance between type 1 and type 2 angiotensin II (Ang II) receptors signaling, leading to liver alterations associated with previously described cardiovascular and kidney disturbances. Chronic administration of a high-lipid diet can provoke an hepatocardiorenal syndrome as the result of activation of the Ang II→type 1 receptor axis, which is completely counteracted by Ang-(3–4) the allosteric enhancer of the Ang II→type 2 receptor pathway.

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.

Angiotensin II type 2 receptor (AT2R) in renal and cardiovascular disease

2016 ◽  
Vol 130 (15) ◽  
pp. 1307-1326 ◽  
Author(s):  
Bryna S.M. Chow ◽  
Terri J. Allen
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Cellular Growth ◽  
Receptor Subtype ◽  
Electrolyte Balance ◽  
Ang Ii ◽  
Biological Responses

Angiotensin II (Ang II) is well-considered to be the principal effector of the renin–angiotensin system (RAS), which binds with strong affinity to the angiotensin II type 1 (AT1R) and type 2 (AT2R) receptor subtype. However, activation of both receptors is likely to stimulate different signalling mechanisms/pathways and produce distinct biological responses. The haemodynamic and non-haemodynamic effects of Ang II, including its ability to regulate blood pressure, maintain water–electrolyte balance and promote vasoconstriction and cellular growth are well-documented to be mediated primarily by the AT1R. However, its biological and functional effects mediated through the AT2R subtype are still poorly understood. Recent studies have emphasized that activation of the AT2R regulates tissue and organ development and provides in certain context a potential counter-regulatory mechanism against AT1R-mediated actions. Thus, this review will focus on providing insights into the biological role of the AT2R, in particular its actions within the renal and cardiovascular system.

Angiotensin II mediates uterine vasoconstriction through α-stimulation

2004 ◽  
Vol 287 (1) ◽  
pp. H126-H134 ◽  
Author(s):  
Blair E. Cox ◽  
Timothy A. Roy ◽  
Charles R. Rosenfeld
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Pressor Responses ◽  
Adrenergic Activation

Intravenous angiotensin II (ANG II) increases uterine vascular resistance (UVR), whereas uterine intra-arterial infusions do not. Type 2 ANG II (AT2) receptors predominate in uterine vascular smooth muscle; this may reflect involvement of systemic type 1 ANG II (AT1) receptor-mediated α-adrenergic activation. To examine this, we compared systemic pressor and UVR responses to intravenous phenylephrine and ANG II without and with systemic or uterine α-receptor blockade and in the absence or presence of AT1 receptor blockade in pregnant and nonpregnant ewes. Systemic α-receptor blockade inhibited phenylephrine-mediated increases in mean arterial pressure (MAP) and UVR, whereas uterine α-receptor blockade alone did not alter pressor responses and resulted in proportionate increases in UVR and MAP. Although neither systemic nor uterine α-receptor blockade affected ANG II-mediated pressor responses, UVR responses decreased >65% and also were proportionate to increases in MAP. Systemic AT1 receptor blockade inhibited all responses to intravenous ANG II. In contrast, uterine AT1 receptor blockade + systemic α-receptor blockade resulted in persistent proportionate increases in MAP and UVR. Uterine AT2 receptor blockade had no effects. We have shown that ANG II-mediated pressor responses reflect activation of systemic vascular AT1 receptors, whereas increases in UVR reflect AT1 receptor-mediated release of an α-agonist and uterine autoregulatory responses.

Chronic administration of nitric oxide reduces angiotensin II receptor type 1 expression and aldosterone synthesis in zona glomerulosa cells

2004 ◽  
Vol 287 (5) ◽  
pp. E820-E827 ◽  
Author(s):  
Kasem Nithipatikom ◽  
Blythe B. Holmes ◽  
Michael J. McCoy ◽  
Cecilia J. Hillard ◽  
William B. Campbell
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Chronic Administration ◽  
Zona Glomerulosa ◽  
Side Chain ◽  
Ang Ii ◽  
At1 Receptors ◽  
Chain Cleavage ◽  
Cleavage Enzyme

Acute nitric oxide (NO) inhibits angiotensin II (ANG II)-stimulated aldosterone synthesis in zona glomerulosa (ZG) cells. In this study, we investigated the effects of chronic administration of NO on the ANG II receptor type 1 (AT1) expression and aldosterone synthesis. ZG cells were treated daily with DETA NONOate (10−4 M), an NO donor, for 0, 12, 24, 48, 72, and 96 h. Chinese hamster ovary (CHO) cells, stably transfected with the AT1B receptor, were used as a positive control. Western blot analysis indicated that AT1 receptor expression was decreased as a function of time of NO administration in both CHO and ZG cells. ANG II binding to its receptors was determined by radioligand binding. NO treatment of ZG cells for 96 h resulted in a decrease in ANG II binding compared with control. The receptor density was decreased to 1,864 ± 129 fmol/mg protein from 3,157 ± 220 fmol/mg protein ( P < 0.005), but the affinity was not changed (1.95 ± 0.22 vs. 1.88 ± 0.21 nM). Confocal Raman microspectroscopy and immunocytochemistry both confirmed that the expression of AT1 receptors in ZG cells decreased with chronic NO administration. In addition, chronic NO administration also decreased the expression of cholesterol side-chain cleavage enzyme in ZG cells and inhibited ANG II- and 25-hydroxycholesterol-stimulated aldosterone synthesis in ZG cells. This study demonstrates that chronic administration of NO inhibits aldosterone synthesis in ZG cells by downregulation of the expression of both AT1 receptors and cholesterol side-chain cleavage enzyme.

scholarly journals Localized accumulation of angiotensin II and production of angiotensin-(1–7) in rat luteal cells and effects on steroidogenesis

2006 ◽  
Vol 291 (2) ◽  
pp. E221-E233 ◽  
Author(s):  
John R. Pepperell ◽  
Gabor Nemeth ◽  
Yuji Yamada ◽  
Frederick Naftolin ◽  
Maricruz Merino
Keyword(s):  
Angiotensin Ii ◽  
Inhibitory Effect ◽  
Ang Ii ◽  
Luteal Cells ◽  
Permeabilized Cells ◽  
Production Studies ◽  
Progesterone Production ◽  
Angiotensin Peptides

These studies aim to investigate subcellular distribution of angiotensin II (ANG II) in rat luteal cells, identify other bioactive angiotensin peptides, and investigate a role for angiotensin peptides in luteal steroidogenesis. Confocal microscopy showed ANG II distributed within the cytoplasm and nuclei of luteal cells. HPLC analysis showed peaks that eluted with the same retention times as ANG-(1–7), ANG II, and ANG III. Their relative concentrations were ANG II ≥ ANG-(1–7) > ANG III, and accumulation was modulated by quinapril, an inhibitor of angiotensin-converting enzyme (ACE), Z-proprolinal (ZPP), an inhibitor of prolyl endopeptidase (PEP), and parachloromercurylsulfonic acid (PCMS), an inhibitor of sulfhydryl protease. Phenylmethylsulfonyl fluoride (PMSF), a serine protease inhibitor, did not affect peptide accumulation. Quinapril, ZPP, PCMS, and PMSF, as well as losartan and PD-123319, the angiotensin receptor type 1 (AT1) and type 2 (AT2) receptor antagonists, were used in progesterone production studies. ZPP significantly reduced luteinizing hormone (LH)-dependent progesterone production ( P < 0.05). Quinapril plus ZPP had a greater inhibitory effect on LH-stimulated progesterone than either inhibitor alone, but this was not reversed by exogenous ANG II or ANG-(1–7). Both PCMS and PMSF acutely blocked LH-stimulated progesterone, and PCMS blocked LH-sensitive cAMP accumulation. Losartan inhibited progesterone production in permeabilized but not intact luteal cells and was reversed by ANG II. PD-123319 had no significant effect on luteal progesterone production in either intact or permeabilized cells. These data suggest that steroidogenesis may be modulated by angiotensin peptides that act in part through intracellular AT1 receptors.

Role of 12-lipoxygenase in decreasing P-cadherin and increasing angiotensin II type 1 receptor expression according to glomerular size in type 2 diabetic rats

2011 ◽  
Vol 300 (4) ◽  
pp. E708-E716 ◽  
Author(s):  
Qiao-Yan Guo ◽  
Li-Ning Miao ◽  
Bing Li ◽  
Fu-Zhe Ma ◽  
Nian Liu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Diabetic Rats ◽  
Ang Ii ◽  
Direct Infusion ◽  
Protein Expressions ◽  
12 Lipoxygenase ◽  
Type 2 Diabetic

12-lipoxygenase (12-LO) was implicated in the development of diabetic nephropathy (DN), in which the proteinuria was thought to be associated with a decreased expression of glomerular P-cadherin. Therefore, we investigated the role of 12-LO in the glomerular P-cadherin expression in type 2 diabetic rats according to the glomerular sizes. Rats fed with high-fat diet for 6 wk were treated with low-dose streptozotocin. Once diabetes onset, diabetic rats were treated with 12-LO inhibitor cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC) for 8 wk. Then glomeruli were isolated from diabetic and control rats with a sieving method. RT-PCR, Western blotting, and immunofluorescent staining were used for mRNA and protein expressions of P-cadherin and angiotensin II (Ang II) type 1 receptor (AT1). We found that CDC did not affect the glucose levels but completely attenuated diabetic increases in glomerular volume and proteinuria. Diabetes significantly decreased the P-cadherin mRNA and protein expressions and increased the AT1 mRNA and protein expressions in the glomeruli. These changes were significantly prevented by CDC and recaptured by direct infusion of 12-LO product [12(S)-HETE] to normal rats for 7 days. The decreased P-cadherin expression was similar between large and small glomeruli, but the increased AT1 expression was significantly higher in the large than in the small glomeruli from diabetic and 12(S)-HETE-treated rats. Direct infusion of normal rats with Ang II for 14 days also significantly decreased the glomerular P-cadherin expression. These results suggest that diabetic proteinuria is mediated by the activation of 12-LO pathway that is partially attributed to the decreased glomerular P-cadherin expression.

Angiotensin II receptors are expressed and functional in human esophageal mucosa

2009 ◽  
Vol 297 (5) ◽  
pp. G1019-G1027 ◽  
Author(s):  
Anna Casselbrant ◽  
Anders Edebo ◽  
Peter Hallersund ◽  
Emma Spak ◽  
Herbert F. Helander ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ion Transport ◽  
Receptor Antagonist ◽  
Ussing Chamber ◽  
Renin Angiotensin System ◽  
Esophageal Mucosa ◽  
Ang Ii

Only few studies have been devoted to the actions of the renin-angiotensin system (RAS) in the human gastrointestinal tract. The present study was undertaken to elucidate the expression and action of RAS in the human esophageal mucosa. Mucosal specimens with normal histological appearance were obtained from healthy subjects undergoing endoscopy and from patients undergoing esophagectomy due to neoplasm. Gene and protein expressions of angiotensin II (Ang II) receptor type 1 (AT1) and type 2 (AT2) and angiotensin-converting enzyme (ACE) were analyzed. In vivo functionality in healthy volunteers was reflected by assessing transmucosal potential difference (PD). Ussing chamber technique was used to analyze the different effects of Ang II on its AT1 and AT2 receptors. Immunoreactivity to AT1 and AT2 was localized to stratum superficiale and spinosum in the epithelium. ACE, AT1, and AT2 were found in blood vessel walls. Transmucosal PD in vivo increased following administration of the AT1 receptor antagonist candesartan. In Ussing preparations mean basal transmural PD was −6.4 mV, epithelial current ( Iep) 34 μA/cm2, and epithelial resistance ( Rep) 321 Ω·cm2. Serosal exposure to Ang II increased PD as a result of increased Iep, whereas Rep was constant. Ang II given together with the selective AT1-receptor antagonist losartan, or AT2 agonist C21 given alone, resulted in a similar effect. Ang II given in presence of the AT2-receptor antagonist PD123319 did not influence PD, but Iep decreased and Rep increased. In conclusion, Ang II receptors and ACE are expressed in the human esophageal epithelium. The results suggest that AT2-receptor stimulation increases epithelial ion transport, whereas the AT1 receptor inhibits ion transport and increases Rep.

scholarly journals Renal microvascular actions of angiotensin II fragments

2002 ◽  
Vol 283 (1) ◽  
pp. F86-F92 ◽  
Author(s):  
William F. van Rodijnen ◽  
Ton A. van Lambalgen ◽  
Michiel H. van Wijhe ◽  
Geert-Jan Tangelder ◽  
Piet M. ter Wee
Keyword(s):  
Angiotensin Ii ◽  
Receptor Blocker ◽  
Ang Ii ◽  
Antagonistic Action ◽  
Afferent Arterioles ◽  
High Concentrations ◽  
Ang Iv ◽  
Rat Kidneys

In the present study, we investigated renal microvascular responses to ANG-(1–7) and ANG IV. Diameter changes of small interlobular arteries, afferent arterioles, and efferent arterioles were assessed by using isolated perfused hydronephrotic rat kidneys. ANG-(1–7) and ANG IV concentration dependently decreased the diameters of all investigated renal microvessel, however, with a much lower potency than ANG II. The ANG II type 1 receptor blocker irbesartan completely reversed the responses to ANG-(1–7) and ANG IV, whereas the ANG II type 2 receptor blocker PD-123319 had no effect. Both ANG-(1–7) and ANG IV failed to alter renal microvascular constriction induced by ANG II. In addition, subnanomolar concentrations of ANG-(1–7) had no effect on the myogenic-induced tone of interlobular arteries and afferent arterioles. Thus our data indicate that at high concentrations, ANG-(1–7) and ANG IV are able to activate the ANG II type 1 receptor, thereby inducing renal microvascular constriction. The failure of ANG-(1–7) and ANG IV to reduce ANG II- and pressure-induced constrictions suggests that these fragments do not exert a vasodilator and/or ANG II antagonistic action in the kidney.

The angiotensin II type 2 receptor: an enigma with multiple variations

2000 ◽  
Vol 278 (3) ◽  
pp. E357-E374 ◽  
Author(s):  
Stefan Gallinat ◽  
Silke Busche ◽  
Mohan K. Raizada ◽  
Colin Sumners
Keyword(s):  
Angiotensin Ii ◽  
Singular Function ◽  
Ang Ii ◽  
Experimental Approaches ◽  
Number Of Publications ◽  
Cardiovascular Functions ◽  
Made In

Since it was discovered ten years ago, the angiotensin II (ANG II) type 2 (AT2) receptor has been an enigma. This receptor binds ANG II with a high affinity but is not responsible for mediating any of the classical physiological actions of this peptide, all of which involve the ANG II type 1 (AT1) receptor. Furthermore, the AT2 receptor exhibits dramatic differences in biochemical and functional properties and in patterns of expression compared with the AT1 receptor. During the past decade, much information has been gathered about the AT2 receptor, and the steadily increasing number of publications indicates a growing interest in this new and independent area of research. A number of studies suggest a role of AT2 receptors in brain, renal, and cardiovascular functions and in the processes of apoptosis and tissue regeneration. Despite these advances, nothing stands out as the major singular function of these receptors. The study of AT2 receptors has reached a crossroads, and innovative approaches must be considered so that unifying mechanisms as to the function of these unique receptors can be put forward. In this review we will discuss the advances that have been made in understanding the biology of the AT2receptor. Furthermore, we will consider how these discoveries, along with newer experimental approaches, may eventually lead to the elusive physiological and pathophysiological functions of these receptors.

scholarly journals Involvement of angiotensin II and beta-adrenergic receptors in the regulation of autophagy in human endothelial EA.hy926 cell line

2020 ◽  
Vol 19 (4) ◽  
pp. 751-757
Author(s):  
Moon Jain ◽  
Prasanna K. Sahu ◽  
Kashif Hanif
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Cell Line ◽  
Adrenergic Receptors ◽  
Autophagic Flux ◽  
Ang Ii ◽  
Β Adrenergic Receptors

Purpose: To investigate the role of angiotensin II (Ang II) and β adrenergic receptors (βARs) in autophagy regulation in human endothelial EA.hy926 cell line.Methods: The effect of pharmacological modulation of Ang II receptors and βARs on the expression of LC3B-II and p62 proteins (autophagosome formation marker and autophagic flux marker, respectively) in the human endothelial EA.hy926 cell line were investigated by immunoblotting technique.Results: Ang II-induced autophagy was characterized by increased LC3B-II and reduced p62 expressions. Candesartan, an AT1R agonist,  significantly suppressed the effects of Ang II, while a selective AT2R antagonist, PD123319, inhibited the effect of candesartan. An AT2R agonist, CGP-42112A, also suppressed the Ang II-induced autophagy. Treatment with isoproterenol enhanced the expression of LC3B-II and reduced that of p62; these effects were suppressed upon cotreatment with propranolol (non-selective βAR blocker propranolol). A selective β1AR agonist, dobutamine, reduced the expression of LC3B-II, and increased that of p62; the same was suppressed upon treatment with a selective β1AR antagonist, metoprolol. A selective β2AR agonist, salbutamol, resulted in increased expression of LC3B-II and reduced expression of p62. These effects were encountered upon treatment with selective β2AR antagonist, ICI-118,551.Conclusion: Based on the foregoing, it is evident that AT1Rs mediates Ang II-induced endothelial cell autophagy, while AT2Rs antagonizes the mechanism. βAR activation mediates isoproterenol-induced endothelial cell autophagy, which results from the balance of β1ARs-mediated suppression and β2ARsmediated upregulation of autophagy in the endothelial cells. Keywords: Autophagy, Angiotensin II type 1 receptors, Angiotensin II type 2 receptors β adrenergic type 1 receptors, β adrenergic type 2 receptors endothelial cells

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