scholarly journals ASPECTOS FUNCIONAIS E FISIOLÓGICOS DO SISTEMA RENINA-ANGIOTENSINA ALDOSTERONA

2016 ◽  
Vol 7 (1) ◽  
pp. 1-15
Author(s):  
Dione Rodrigues Fernandes ◽  
Roberto Dantas Cavalcante Filho ◽  
Jucélia Da Silva Nunes ◽  
Vera Lúcia Matias Gomes Geron ◽  
André Tomaz Terra Júnior
Keyword(s):  
Ang Ii ◽  
Ang Iv

O Sistema Renina AngiotensinaAldosterona (SRAA) exerce um papel muito importante na homeostase cardiovascular, desempenhando uma função primordial no controle dinâmico da volemia e da resistência vascular periférica. O SRAA representa um alvo importante no tratamento da hipertensão arterial humana. Em resposta à diminuição do volume sanguíneo efetivo, a renina é liberada na circulação sanguínea através do aparelho justaglomerular localizado nos rins fazendo com que ela catalisa a conversão do Angiotensinogênio (AGT), liberado pelo fígado, em Angiotensina I (ANG I) que, ao entrar em contato com a Enzima Conversora da Angiotensina (ECA) situada na superfície do endotélio pulmonar, é convertida no peptídeo efetor Angiotensina II (ANG II). Para exercer sua atividade biológica, a ANG II liga-se, preferencialmente, ao receptor de alta afinidade AT1 existente em uma variedade de tecidos. Entretanto, o Sistema Renina Angiotensina (SRA) também tem sido identificado em diversos órgãos e, mais recentemente, novo estudos têm mostrado a presença desse sistema intracelular. Outros peptídeos do SRA parecem ter ações biológicas como a Angiotensina III (ANG III), Angiotensina IV (ANG IV), Angiotensina 1-7 (ANG 1-7) e a Angiotensina 1-9 (ANG 1-9). O presente estudo bibliográfico teve como objetivo principal descrever o sistema renina angiotensina aldosterona SRAA, evidenciando as suas funções dentro das possíveis alterações fisiopatológicas que podem ocorrer no organismo, objetivando estabelecer a homeostasia dentro da normalidade fisiológica.

scholarly journals Development of a novel nanoflow liquid chromatography-parallel reaction monitoring mass spectrometry-based method for quantification of angiotensin peptides in HUVEC cultures

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9941
Author(s):  
Chuan He ◽  
Simiao Hu ◽  
Wanxing Zhou
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Culture Supernatant ◽  
Reaction Monitoring ◽  
Ang Ii ◽  
Parallel Reaction ◽  
Parallel Reaction Monitoring ◽  
Relative Standard ◽  
Ang Iv ◽  
Nanoflow Liquid Chromatography

Background This study aimed to develop an analytical method using liquid chromatography tandem mass spectrometry (LC-MS/MS) for the determination of angiotensin (Ang) I, Ang (1-9), Ang II, Ang (1-7), Ang (1-5), Ang III, Ang IV in human umbilical vein endothelial cell (HUVEC) culture supernatant. Methods HUVEC culture supernatant was added with gradient concentrations (0.05–1,000 ng/ml) of standard solutions of the Ang peptides. These samples underwent C18 solid-phase extraction and separation using a preconcentration nano-liquid chromatography mass spectrometry system. The target peptides were detected by a Q Exactive quadrupole orbitrap high-resolution mass spectrometer in the parallel reaction monitoring mode. Ang converting enzyme (ACE) in HUVECs was silenced to examine Ang I metabolism. Results The limit of detection was 0.1 pg for Ang II and Ang III, and 0.5 pg for Ang (1-9), Ang (1-7), and Ang (1-5). The linear detection range was 0.1–2,000 pg (0.05–1,000 ng/ml) for Ang II and Ang III, and 0.5–2,000 pg (0.25–1,000 ng/ml) for Ang (1-9) and Ang (1-5). Intra-day and inter-day precisions (relative standard deviation) were <10%. Ang II, Ang III, Ang IV, and Ang (1-5) were positively correlated with ACE expression by HUVECs, while Ang I, Ang (1-7), and Ang (1-9) were negatively correlated. Conclusion The nanoflow liquid chromatography-parallel reaction monitoring mass spectrometry-based methodology established in this study can evaluate the Ang peptides simultaneously in HUVEC culture supernatant.

scholarly journals The Biochemical Effects of Angiotensin-(1-7) on the Oxidative Stress Metabolism and Their Specific Parameters from the Temporal Lobe

2020 ◽  
Vol 71 (6) ◽  
pp. 307-311
Author(s):  
Sorin Ungurianu ◽  
Constantin Trus ◽  
Roxana-Rosmary Enciu
Keyword(s):  
Oxidative Stress ◽  
Temporal Lobe ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
Vascular Area ◽  
Ang Iv ◽  
The One

It is already known from a variety of previous reports that an independent brain renin�angiotensin system (RAS) exists, completely separated from the one in the periphery. This independent brain RAS has all the precursors and the enzymatic structures necessary for the generation of the angiotensin peptides. Thus, in the last few years various groups started focusing on the more central effects of less known angiotensins (e.g in comparison with Angiotensin (Ang) II), namely Ang III, Ang IV, Ang-(1�7) or Ang 5-8. One of these newly emerging angiotensins which has become an increased center of interest in many studies is Ang-(1-7), which is a heptapeptide previously described especially for its opposite effects to Ang II, in the peripheral vascular area, but also described for some opposite central functions vs. Ang II. These aspects are completed with the fact that it was recently suggested that the renin�angiotensin system could modulate the oxidative stress metabolism, and also it seems that the manifestations of Angiotensin-(1-7) on the basal oxidative stress status are contradictory, with a variety of reports describing controversial (e.g. both pro-oxidant and antioxidant actions) effects for this heptapeptide. Our results presented here are confirming a possible antioxidant effect of Ang-(1�7) administration on rat, as shown by the increased levels of antioxidant enzymes from the temporal lobe (superoxide dismutase and glutathione peroxidase) and decreased levels of malondialdehyde, as an important lipid peroxidation parameter.

scholarly journals Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
P. P. Wołkow ◽  
B. Bujak-Giżycka ◽  
J. Jawień ◽  
R. Olszanecki ◽  
J. Madej ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Complications ◽  
Rat Aorta ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Classical Pathway ◽  
Ang Ii ◽  
Liquid Chromatography Mass Spectrometry ◽  
Angiotensin I ◽  
Ang Iv

Purpose. Products of angiotensin (ANG) I metabolism may predispose to vascular complications of diabetes mellitus. Methods. Diabetes was induced with streptozotocin (75 mg/kg i.p.). Rat aorta fragments, isolated 4 weeks later, were pretreated with perindoprilat (3 μM), thiorphan (3 μM), or vehicle and incubated for 15 minutes with ANG I (1 μM). Products of ANG I metabolism through classical (ANG II, ANG III, and ANG IV) and alternative (ANG (1–9), ANG (1–7), and ANG (1–5)) pathways were measured in the buffer, using liquid chromatography-mass spectrometry. Results. Incubation with ANG I resulted in higher concentration of ANG II (P = 0.02, vehicle pretreatment) and lower of ANG (1–9) (P=0.048, perindoprilat pretreatment) in diabetes. Preference for the classical pathway is suggested by higher ANG III/ANG (1–7) ratios in vehicle (P=0.03), perindoprilat (P=0.02), and thiorphan pretreated (P=0.02) diabetic rat. Within the classical pathway, ratios of ANG IV/ANG II (P=0.01) and of ANG IV/ANG III (P=0.049), but not of ANG III/ANG II are lower in diabetes. Conclusions. Diabetes in rats led to preference toward deleterious (ANG II, ANG III) over protective (ANG IV, ANG (1–9), and ANG (1–7)) ANG I metabolites.

Effects of different angiotensins during acute, double blockade of the renin system in conscious dogs

2003 ◽  
Vol 285 (5) ◽  
pp. R971-R980 ◽  
Author(s):  
Christian Wamberg ◽  
Ronni R. Plovsing ◽  
Niels C. F. Sandgaard ◽  
Peter Bie
Keyword(s):  
Blood Pressure ◽  
Biological Activity ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Dose Response ◽  
Filtration Rate ◽  
Conscious Dogs ◽  
Ang Ii ◽  
Aldosterone Secretion ◽  
Ang Iv

Evidence of biological activity of fragments of ANG II is accumulating. Fragments considered being inactive degradation products might mediate actions previously attributed to ANG II. The study aimed to determine whether angiotensin fragments exert biological activity when administered in amounts equimolar to physiological doses of ANG II. Cardiovascular, endocrine, and renal effects of ANG II, ANG III, ANG IV, and ANG-(1-7) (6 pmol·kg-1·min-1) were investigated in conscious dogs during acute inhibition of angiotensin I-converting enzyme (enalaprilate) and aldosterone (canrenoate). Furthermore, ANG III was investigated by step-up infusion (30 and 150 pmol·kg-1·min-1). Arterial plasma concentrations [ANG immunoreactivity (IR)] were determined by an ANG II antibody cross-reacting with ANG III and ANG IV. Metabolic clearance rates were higher for ANG III and ANG IV (391 ± 19 and 274 ± 13 ml·kg-1·min-1, respectively) than for ANG II (107 ± 13 ml·kg-1·min-1). ANG II increased ANG IR by 60 ± 7 pmol/ml, blood pressure by 30%, increased plasma aldosterone markedly (to 345 ± 72 pg/ml), and plasma vasopressin transiently, while reducing glomerular filtration rate (40 ± 2 to 33 ± 2 ml/min), sodium excretion (50 ± 7 to 16 ± 4 μmol/min), and urine flow. Equimolar amounts of ANG III induced similar antinatriuresis (57 ± 8 to 19 ± 3 μmol/min) and aldosterone secretion (to 268 ± 71 pg/ml) at much lower ANG IR increments (∼1/7) without affecting blood pressure, vasopressin, or glomerular filtration rate. The effects of ANG III exhibited complex dose-response relations. ANG IV and ANG-(1-7) were ineffective. It is concluded that 1) plasma clearances of ANG III and ANG IV are higher than those of ANG II; 2) ANG III is more potent than ANG II in eliciting immediate sodium and potassium retention, as well as aldosterone secretion, particularly at low concentrations; and 3) the complexity of the ANG III dose-response relationships provides indirect evidence that several effector mechanisms are involved.

scholarly journals Effects of truncated angiotensins in humans after double blockade of the renin system

2003 ◽  
Vol 285 (5) ◽  
pp. R981-R991 ◽  
Author(s):  
Ronni R. Plovsing ◽  
Christian Wamberg ◽  
Niels C. F. Sandgaard ◽  
Jane A. Simonsen ◽  
Niels-Henrik Holstein-Rathlou ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Biological Activities ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Urinary Concentration ◽  
Ang Ii ◽  
Ang Iv

Angiotensins different from ANG II exhibit biological activities, possibly mediated via receptors other than ANG II receptors. We studied the effects of 3-h infusions of ANG III, ANG-(1-7), and ANG IV in doses equimolar to physiological amounts of ANG II (3 pmol · kg-1 · min-1), in six men on low-sodium diet (30 mmol/day). The subjects were acutely pretreated with canrenoate and captopril to inhibit aldosterone actions and ANG II synthesis, respectively. ANG II infusion increased plasma angiotensin immunoreactivity to 53 ± 6 pg/ml (+490%), plasma aldosterone to 342 ± 38 pg/ml (+109%), and blood pressure by 27%. Glomerular filtration rate decreased by 16%. Concomitantly, clearance of endogenous lithium fell by 66%, and fractional proximal reabsorption of sodium increased from 77 to 92%; absolute proximal reabsorption rate of sodium remained constant. ANG II decreased sodium excretion by 70%, potassium excretion by 50%, and urine flow by 80%, whereas urine osmolality increased. ANG III also increased plasma aldosterone markedly (+45%), however, without measurable changes in angiotensin immunoreactivity, glomerular filtration rate, or renal excretion rates. During vehicle infusion, plasma renin activity decreased markedly (∼700 to ∼200 mIU/l); only ANG II enhanced this decrease. ANG-(1-7) and ANG IV did not change any of the measured variables persistently. It is concluded that 1) ANG III and ANG IV are cleared much faster from plasma than ANG II, 2) ANG II causes hypofiltration, urinary concentration, and sodium and potassium retention at constant plasma concentrations of vasopressin and atrial natriuretic peptide, and 3) a very small increase in the concentration of ANG III, undetectable by usual techniques, may increase aldosterone secretion substantially.

scholarly journals Discovery of Inhibitors of Insulin-Regulated Aminopeptidase as Cognitive Enhancers

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Hanna Andersson ◽  
Mathias Hallberg
Keyword(s):  
Intracerebroventricular Injection ◽  
Binding Affinities ◽  
Ang Ii ◽  
Angiotensin Iv ◽  
Positive Effects ◽  
Main Target ◽  
The Status ◽  
Ang Iv ◽  
The Relationship ◽  
The Brain

The hexapeptide angiotensin IV (Ang IV) is a metabolite of angiotensin II (Ang II) and plays a central role in the brain. It was reported more than two decades ago that intracerebroventricular injection of Ang IV improved memory and learning in the rat. Several hypotheses have been put forward to explain the positive effects of Ang IV and related analogues on cognition. It has been proposed that the insulin-regulated aminopeptidase (IRAP) is the main target of Ang IV. This paper discusses progress in the discovery of inhibitors of IRAP as potential enhancers of cognitive functions. Very potent inhibitors of the protease have been synthesised, but pharmacokinetic issues (including problems associated with crossing the blood-brain barrier) remain to be solved. The paper also briefly presents an overview of the status in the discovery of inhibitors of ACE and renin, and of AT1R antagonists and AT2R agonists, in order to enable other discovery processes within the RAS system to be compared. The paper focuses on the relationship between binding affinities/inhibition capacity and the structures of the ligands that interact with the target proteins.

scholarly journals AT1 receptor-activated signaling mediates angiotensin IV-induced renal cortical vasoconstriction in rats

2006 ◽  
Vol 290 (5) ◽  
pp. F1024-F1033 ◽  
Author(s):  
Xiao C. Li ◽  
Duncan J. Campbell ◽  
Mitsuru Ohishi ◽  
Shao Yuan ◽  
Jia L. Zhuo
Keyword(s):  
Blood Flow ◽  
Phospholipase C ◽  
Mitogen Activated Protein Kinase ◽  
Classical Type ◽  
Dependent Manner ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Angiotensin Iv ◽  
Ang Iv ◽  
Dose Dependent

Angiotensin IV (ANG IV), an active ANG II fragment, has been shown to induce systemic and renal cortical effects by binding to ANG IV (AT4) receptors and activating unique signaling transductions unrelated to classical type 1 (AT1) or type 2 (AT2) receptors. We tested whether ANG IV exerts systemic and renal cortical effects on blood pressure, renal microvascular smooth muscle cells (VSMCs), and glomerular mesangial cells (MC) and, if so, whether AT1 receptor-activated signaling is involved. In anesthetized rats, systemic infusion of ANG II, ANG III, or ANG IV (0.01, 0.1, and 1.0 nmol·kg−1·min−1 iv) caused dose-dependent increases in mean arterial pressure (MAP) and decreases in renal cortical blood flow (CBF; P < 0.01). ANG II also induced dose-dependent reductions in renal medullary blood flow ( P < 0.01), whereas ANG IV did not. ANG IV-induced pressor and renal cortical vasoconstriction were completely abolished by AT1 receptor blockade with losartan (5 mg/kg iv; P < 0.05). When ANG IV (1 nmol·kg−1·min−1) was infused directly in the renal artery, CBF was reduced by >30%, and the response was also blocked by losartan ( P < 0.01). In the renal cortex, unlabeled ANG IV displaced 125I-labeled [Sar1,Ile8]ANG II binding, whereas unlabeled ANG II (10 μM) inhibited 125I-labeled Nle1-ANG IV (AT4) binding in a concentration-dependent manner ( P < 0.01). In freshly isolated renal VSMCs, ANG IV (100 nM) increased intracellular Ca2+ concentration, and the effect was blocked by losartan and U-73122, a selective inhibitor of phospholipase C/inositol trisphosphate/Ca2+ signaling (1 μM). In cultured rat MCs, ANG IV (10 nM) induced mitogen-activated protein kinase extracellular/signal-regulated kinase 1/2 phosphorylation via AT1 receptor- and phospholipase C-activated signaling. These results suggest that, at nanomolar concentrations, ANG IV can increase MAP and induce renal cortical effects by interacting with AT1 receptor-activated signaling.

Analysis of responses to ANG IV: effects of PD-123319 and DuP-753 in the pulmonary circulation of the rat

1995 ◽  
Vol 268 (2) ◽  
pp. L302-L308 ◽  
Author(s):  
B. D. Nossaman ◽  
C. J. Feng ◽  
A. D. Kaye ◽  
P. J. Kadowitz
Keyword(s):  
Receptor Antagonist ◽  
Pressor Response ◽  
Relative Activity ◽  
Ang Ii ◽  
Vasoactive Peptides ◽  
Angiotensin Peptides ◽  
Acid Fragment ◽  
Pressor Responses ◽  
Ang Iv ◽  
At2 Receptors

Pulmonary vasoconstrictor responses to angiotensin (ANG) IV, the 3-8 amino acid fragment of ANG II, were compared with responses to ANG I, ANG II, and ANG III and to other vasoactive peptides in the isolated blood perfused rat lung. In terms of relative activity, ANG IV was similar in potency to bradykinin and serotonin but was approximately 100-fold less potent than ANG I, ANG II, and ANG III. PD-123319, an AT2-receptor antagonist, enhanced pressor responses to the four angiotensin peptides and to bradykinin but did not significantly change the pressor response to serotonin or to ventilatory hypoxia. DuP-753, an AT1-receptor antagonist, significantly decreased pressor responses to the four angiotensin peptides and enhanced the pressor responses to bradykinin but not to serotonin. Captopril and enalaprilat increased the pressor response to ANG IV. Meclofenamate and N omega-nitro-L-arginine methyl ester shifted the dose-response curve for ANG IV to the left in a manner similar to that observed with ANG II and ANG III. These data show that ANG IV has significant vasoconstrictor activity and suggest that responses are mediated by the activation of AT1 receptors and that vasopressor responses of the angiotensin peptides may be modulated by activation of AT2 receptors. These results also suggest that responses to ANG IV are modulated by the release of vasodilator prostaglandins and nitric oxide and that AT2 receptors have little, if any, role in mediating or modulating the pressor response to ventilatory hypoxia.

Angiotensin IV receptor-mediated activation of lung endothelial NOS is associated with vasorelaxation

1998 ◽  
Vol 275 (6) ◽  
pp. L1061-L1068 ◽  
Author(s):  
Jawaharlal M. Patel ◽  
Jeffrey R. Martens ◽  
Yong D. Li ◽  
Craig H. Gelband ◽  
Mohan K. Raizada ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Blood Flow ◽  
Ang Ii ◽  
Receptor Blockers ◽  
Pulmonary Arterial ◽  
Ang Iv ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Arterial Endothelial Cells

The hexapeptide angiotensin (ANG) IV, a metabolic product of ANG II, has been reported to play a functional role in the regulation of blood flow in extrapulmonary tissues. Here, we demonstrate that ANG IV-specific (AT4) receptors are present in porcine pulmonary arterial endothelial cells (PAECs) and that the binding of ANG IV to AT4 receptors can be blocked by its antagonist divalinal ANG IV but not by the ANG II-, AT1-, and AT2-receptor blockers [Sar1,Ile8]ANG II, losartan, and PD-123177, respectively. ANG IV significantly increased endothelial cell constitutive nitric oxide synthase (ecNOS) activity ( P < 0.05) as well as cellular cGMP content ( P < 0.001). Western blot analysis revealed that ecNOS protein expression was comparable in control and ANG IV-stimulated cells. Divalinal ANG IV but not [Sar1,Ile8]ANG II, losartan, or PD-123177 inhibited the ANG II- and ANG IV-stimulated increases in ecNOS activity and cGMP content in PAECs. Incubation in the presence of N-nitro-l-arginine methyl ester (l-NAME) or methylene blue but not of indomethacin significantly diminished ANG IV-stimulated as well as basal levels of cGMP ( P < 0.001). Similarly, in situ studies with precontracted porcine pulmonary arterial rings showed that ANG IV caused an endothelium-dependent relaxation that was blocked byl-NAME or methylene blue. Collectively, these results demonstrate that ANG IV binds to AT4 receptors, activates ecNOS by posttranscriptional modulation, stimulates cGMP accumulation in PAECs, and causes pulmonary arterial vasodilation, suggesting that ANG IV plays a role in the regulation of blood flow in the pulmonary circulation.

Stimulation of DNA and RNA Synthesis in Cultured Rabbit Cardiac Fibroblasts by Angiotensin IV

1995 ◽  
Vol 88 (5) ◽  
pp. 557-562 ◽  
Author(s):  
L. Wang ◽  
M. Eberhard ◽  
P. Erne
Keyword(s):  
Rna Synthesis ◽  
Cardiac Fibroblasts ◽  
Leucine Incorporation ◽  
Ang Ii ◽  
Angiotensin Iv ◽  
Single Class ◽  
Dna And Rna ◽  
Dna And Rna Synthesis ◽  
Ang Iv ◽  
Stimulation Of

1. Although angiotensin II (ANG II) has been identified as a key factor in the development of cardiac hypertrophy and remodelling, the role of its degradation fragment ANG II (3–8), angiotensin IV (ANG IV), is unknown. The presence of ANG IV in the blood circulation as well as the identification of ANG IV receptors in the heart and other organs indicates that ANG IV may act as a peptide hormone. 2. ANG IV receptors were characterized by binding of 125I-ANG IV to membranes of cultured rabbit cardiac fibroblasts. Incorporation of [3H]thymidine, [3H]uridine and [3H]Ieucine into DNA, RNA and proteins, respectively, was determined to analyse the growth effects of ANG IV, ANG II and the combination of both peptides. 3. ANG IV displaces 125I-ANG IV bound to membranes of rabbit cardiac fibroblasts with high affinity, whereas ANG II receptor-specific ligands ([Sar1,Ile8]ANG II, losartan, CGP 42 112 A) do not. 125I-ANG IV binds to a single class of binding site with a dissociation constant (Kd) of 4.87 ± 0.11 nmol/l. The density of ANG IV receptors (Bmax.) is 371 ± 8.3 fmol/mg of protein. 125I-ANG IV binding is not markedly affected in the presence of the non-hydrolysable GTP analogue GTPγS, whereas binding of 125I-ANG II is reduced. 4. In quiescent cells, a 24 h exposure of ANG IV (100 nmol/l) increased rates of thymidine and uridine incorporation by 127% and 246%, respectively. A small but statistically insignificant increase in leucine incorporation was observed under these conditions. Similar effects have been observed after stimulation by ANG II (100 nmol/l, 24 h). The combination of ANG II and ANG IV has additive effects on uridine, but not on thymidine and leucine incorporation. 5. In conclusion, rabbit cardiac fibroblasts express a specific ANG IV receptor, distinct from the known ANG II receptors, which mediates the stimulation of cellular DNA and RNA synthesis.

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