AT1 Receptor; AT2 Receptor

Angiotensin II human (Ang II) is recognized to have most of its actions through AT1 receptors, whereas AT2 receptors assist in controlling blood pressure and renal function [1]. Human angiotensin II elevates blood pressure (BP) by a number of mechanisms, the most significant of which are renal effects, sympathetic activation, vasoconstriction, and enhanced aldosterone production. Other human effects of angiotensin II include promotion of growth, cell migration, and mitosis in vascular smooth muscle cells, increased production of type I and type III collagen in fibroblasts, leading to thickening of vessel walls and myocardium, and fibrosis. Ang II receptor type 1 (AT1) mediates these actions [2]. Angiotensin II (1 nM) TFA promotes capillary development in human coronary artery endothelial cells and increases the production of LOX-1 and VEGF in the Matrigel assay. Apocynin, a glycolate phosphate oxidase inhibitor, and losartan, an Ang II type 1 receptor blocker, all inhibit angiotensin II-mediated VEGF and LOX-1 expression, capillary formation, intracellular reactive oxygen species production, and phosphorylation of p38 and p44/42 mitogen-activated protein kinase dinuclear [3]. The Ang II type 2 receptor blocker PD123319 is not inhibited by the anti-LOX-1 antibody nicotinamide adenine.

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Angiotensin II (Ang II) induces angiogenesis by stimulating reactive oxygen species-dependent vascular endothelial growth factor (VEGF) expression. Ang II via type 1 receptor upregulates the expression of LOX-1, a lectin-like receptor for oxidized low-density lipoprotein. LOX-1 activation, in turn, upregulates Ang II type 1 receptor expression. We postulated that interruption of the feedback loop between Ang II and LOX-1 might attenuate Ang II-induced VEGF expression and capillary formation. In vitro experiments showed that Ang II (1 nmol/L) induced the expression of LOX-1 and VEGF and enhanced capillary formation from human coronary endothelial cells in Matrigel assay. Ang II-mediated expression of LOX-1 and VEGF, capillary formation, intracellular reactive oxygen species generation, and phosphorylation of p38 as well as p44/42 mitogen-activated protein kinases, were suppressed by anti-LOX-1 antibody, nicotinamide-adenine dinucleotide phosphate oxidase inhibitor apocynin and the Ang II type 1 receptor blocker losartan, but not by the Ang II type 2 receptor blocker PD123319. Expression of VEGF and capillary formation induced by Ang II were also inhibited by the p44/42 mitogen-activated protein kinase inhibitor U0126 and the p38 mitogen-activated protein kinase inhibitor SB203580. In ex vivo experiments, Ang II stimulated capillary sprouting from aortic rings from wild-type mice, and this phenomenon was significantly attenuated by pretreatment of aortic rings with anti-LOX-1 antibody, apocynin, and losartan, but not by PD123319. Importantly, Ang II-induced capillary sprouting was minimal from aortic rings from LOX-1 null mice compared with wild-type mice. These findings suggest that small concentrations of Ang II promote capillary formation by inducing the expression of VEGF via Ang II type 1 receptor/LOX-1-mediated stimulation of the reactive oxygen species-mitogen-activated protein kinase pathway [3].

Angiotensin II human can be used to establish animal models of hypertension and cardiac hypertrophy.

Hypertension Model Induction
Mechanism of Action:
Angiotensin II human binds to AT1 receptors, leading to vasoconstriction, sodium and water retention, sympathetic nervous system activation, and oxidative stress, thereby elevating blood pressure.

Experimental Protocol:
• Animal Model: C57/BL6J strain mice • Both sexes • 12-16 weeks old • Body weight 21-27 g
• Dosage Regimen: 800 ng/kg/min dose • 0.003 mL/min flow rate • 7-day duration • Administered via subcutaneous osmotic pump implantation

Notes:
• Sex Differences: Under awake conditions, female mice may exhibit partial resistance to chronic ANG II-induced hypertension, showing less pronounced blood pressure elevation compared to males.

Model Validation Criteria: • Key Indicator: Significant blood pressure increase • On Day 7, male mice show higher BP elevation than females.

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Cardiac Hypertrophy Model Induction
Mechanism of Action:
Angiotensin II human (Ang II) activates AT1 receptors, triggering inflammatory responses, oxidative stress, and extracellular matrix remodeling, ultimately leading to cardiomyocyte proliferation and hypertrophy

Experimental Protocol:
• Animal Model: C57/BL6J strain mice • Male • 8 weeks old
• Dosage Regimen: 2 μg/kg/min dose • 4-week duration • Administered via subcutaneous osmotic pump implantation

Model Validation Criteria:
• Functional Indicators: Significant blood pressure elevation in wild-type (WT) mice
• Morphological Indicators: Cardiac hypertrophy and fibrosis manifestations

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Angiotensin II humans can be utilized in animal modeling to develop cardiovascular and brain illness models. Angiotensin II human (5 mL 1 nM; i.p.; 200-250 g Sprague-Dawley form) produces considerable neutrophil recruitment that is greatest at 4 hours and disappears by 24 hours [4 ]. In order to differentiate the essential AT1 capture skin group, a minipump was placed into each animal, and Angiotensin II human (1000 ng/kg/min) was injected continuously for 4 days. Angiotensin II human induces hypertension by activating AT1 receptors in the kidney to increase salt reabsorption [5].

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Intraperitoneal administration of Angiotensin II/Ang II (1 nmol/L) induced significant neutrophil recruitment within 4 hours (13.3+/-2.3x10(6) neutrophils per rat versus 0.7+/-0.5x10(6) in control animals), which disappeared by 24 hours. Maximal levels of CXC chemokines were detected 1 hour after Ang II injection (577+/-224 pmol/L cytokine-inducible neutrophil chemoattractant [CINC]/keratinocyte-derived chemokine [KC] versus 5+/-3, and 281+/-120 pmol/L macrophage inflammatory protein [MIP-2] versus 14+/-6). Intravital microscopy within the rat mesenteric microcirculation showed that the short-term (30 to 60 minutes) leukocyte-endothelial cell interactions induced by Ang II were attenuated by an anti-rat CINC/KC antibody and nearly abolished by the CXCR2 antagonist SB-517785-M. In human umbilical vein endothelial cells (HUVECs) or human pulmonary artery media in culture, Ang II induced interleukin (IL)-8 mRNA expression at 1, 4, and 24 hours and the release of IL-8 at 4 hours through interaction with Ang II type 1 receptors. When HUVECs were pretreated with IL-1 for 24 hours to promote IL-8 storage in Weibel-Palade bodies, the Ang II-induced IL-8 release was more rapid and of greater magnitude.
Conclusions: Angiotensin II/Ang II provokes rapid neutrophil recruitment, mediated through the release of CXC chemokines such as CINC/KC and MIP-2 in rats and IL-8 in humans, and may contribute to the infiltration of neutrophils observed in acute myocardial infarction.[4]

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Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type I (AT1) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT1 receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that Angiotensin II causes hypertension primarily through effects on AT1 receptors in the kidney. We find that renal AT1 receptors are absolutely required for the development of Angiotensin II-dependent hypertension and cardiac hypertrophy. When AT1 receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT1 receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney [5].

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Angiotensin II human TFA (5 mL 1 nM; intraperitoneal injection; 200-250 g Sprague-Dawley rats) causes a considerable increase in neutrophil recruitment, which peaks at 4 hours and peaks at 24 hours [4]. An osmotic minipump was subcutaneously inserted into each rat to infuse Angiotensin II human TFA (1000 ng/kg/min) for four weeks in order to distinguish AT1 receptor populations that are essential for the etiology of hypertension. Angiotensin II human TFA activates AT1 receptors in the kidney, which increases salt reabsorption and results in hypertension [5].

Experimental Protocols [3]
HCAECs were exposed to Angiotensin IIAng II (0, 0.1, 1, 5, 10, 20, 50, and 100 nmol/L) for 24 hours. In parallel studies, HCAECs were pretreated for 30 minutes with losartan (1, 2, 5, and 10 μmol/L), PD123319 (10 μmol/L), anti–LOX-1 antibody (10 μg/mL), nonspecific IgG (10 μg/mL), apocynin (600 μmol/L), U0126 (10 μmol/L), SB203580 (10 μmol/L), or dimethyl sulfoxide (as vehicle control) before exposure to Ang II. These concentrations and durations of incubation were chosen on the basis of published data9–11 and modified based on pilot experiments.

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Cells or human pulmonary artery media (HPAM) was stimulated with 1 to 1000 nmol/L Angiotensin II/Ang II for 1, 4, 24, or 48 hours. Selective antagonists of Ang II type 1 (AT1; losartan, 10 μmol/L) or type 2 (PD123,319, 10 μmol/L) receptors or a combination of both was added to some wells 1 hour before Ang II (100 nmol/L). Where stated, HUVECs were preincubated with IL-1β (1000 U/mL) for 24 hours to induce synthesis and storage of IL-8 in Weibel-Palade bodies, washed twice, and incubated for 1 hour in fresh medium with or without 1 to 1000 nmol/L Ang II or 100 μmol/L histamine as the positive control. Cycloheximide (0.1 mg/mL) or BAPTA-AM (100 μmol/L) was added to some wells 1 hour before Ang II (100 nmol/L). At the end of the experiment, cell-free supernatants were stored at −20°C for IL-8 ELISA, and HUVECs were washed before digestion in 0.5 mol/L NaOH for determination of protein content by the Lowry procedure or for weighing of the arterial media.[4]

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Quantitative RT-PCR [4]
IL-8 mRNA was determined by real-time quantitative RT–polymerase chain reaction (PCR). HUVECs or HPAM was incubated with medium or 100 nmol/L Angiotensin II/Ang II for 1, 4, or 24 hours, and total RNA was extracted with TRIzol. Quantitative data of relative gene expression were determined by the comparative Ct method (ΔΔCt), as described by the manufacturer (PE-ABI PRISM 7700 sequence detection system) and previously reported. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was the endogenous control gene. TaqMan predevelopment assay reagents were used to determine IL-8 mRNA, and TaqMan RT reagents were used to generate cDNA.

Ex Vivo Studies [3]
Capillary Sprouting From Aortic Rings [3]
Thoracic aortas were isolated from 8-week-old male C57BL/6 mice and LOX-1 null mice anesthetized with pentobarbital sodium (80 mg/kg, IP), cut into 1-mm-thick sections, and embedded in 24-well Matrigel-coated plates. DMEM supplemented with 5% FBS, 20 U/mL of heparin, and penicillin/streptomycin was added to each well of gelled Matrigel. The number and length of microvasculature sprouting from each aortic ring were assessed as described previously.12,13 This study conforms to the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Neutrophil Migration Into the Peritoneal Cavity [4]
Sprague-Dawley rats (200 g to 250 g) were sedated with ether and injected intraperitoneally with 5 mL phosphate-buffered saline (PBS) or 1 nmol/L Angiotensin II/Ang II. After 1, 4, 8, or 24 hours, the rats were killed with an overdose of anesthetic, and the peritoneal cavity was first lavaged with 5 mL PBS and then with 30 mL heparinized (10 U/mL) PBS. The exudates were centrifuged separately to obtain cell pellets and supernatant fluids. The cell pellets were combined for total leukocyte counts in a hemocytometer and differential cell analysis of 500 cells per slide on cytospins stained with May-Grünwald and Giemsa stains. Results are expressed as the number of neutrophils recovered from each cavity. The supernatant from the first (5-mL) lavage was used for determination of total protein content by the Bradford method and, after addition of carrier protein (0.5% bovine serum albumin) and storage at −20°C, for determination of inflammatory mediator concentrations.

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Experimental Protocol [4]
All preparations were left to stabilize for 30 minutes, and baseline (time 0) measurements of leukocyte rolling flux and velocity, leukocyte adhesion, leukocyte emigration, mean arterial blood pressure, centerline red blood cell velocity, shear rate, and venular diameter were obtained. The superfusion buffer was either continued or supplemented with 1 nmol/L Angiotensin II/Ang II. Recordings were performed for 5 minutes at 15-minute intervals for 60 minutes, and the aforementioned leukocyte and hemodynamic parameters were measured. Some animals were pretreated with a polyclonal antibody against rat CINC/KC (10 mg/kg IV at −15 minutes) or with a selective CXCR2 receptor antagonist (SB-517785-M, 25 mg/kg PO at −60 minutes) before Ang II superfusion.

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Experimental Protocol. [5]
Baseline blood pressure measurements were determined on 3 consecutive days while the animals ingested a normal diet containing 0.4% sodium chloride. After these baseline recordings, an osmotic minipump infusing Angiotensin II/Ang II at a rate of 1,000 ng/kg/min was implanted s.c. as described in ref. 23, and blood pressure measurements continued for 21 days.

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Metabolic Balance Studies. [5]
One week after transplantation, the animals were placed in specially designed metabolic cages.The mice were fed 10 gm/day gelled 0.25% NaCl diet that contained all nutrients and water. After 1 week of baseline collections, the animals were implanted with osmotic minipumps infusing Angiotensin II/Ang II as described above and were returned to the metabolic cage for 5 more days. Urinary sodium content was determined by using an IL943 Automatic Flame photometer per the manufacturer's instructions

[1]. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000 Sep;52(3):415-72.

[2]. Role of angiotensin II in blood pressure regulation and in the pathophysiology of cardiovascular disorders. J Hum Hypertens. 1995 Nov;9 Suppl 5:S19-24.

[3]. Angiotensin II induces capillary formation from endothelial cells via the LOX-1 dependent redox-sensitive pathway. Hypertension. 2007;50(5):952-957.

[4]. Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines. Circulation. 2004;110(23):3581-3586.

[5]. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17985-90.

Absorption, Distribution and Excretion
Following the intravenous infusion of angiotensin II in adult patients with septic or other distributive shock, the serum levels of angiotensin II observed were similar at baseline and hour 3 after the intravenous infusion. After 3 hours of treatment, the serum level of angiotensin I (the angiotensin II precursos peptide) is however, reduced by about 40%.
The official prescribing information notes that no specific studies have been conducted that examine the elimination of angiotensin II.
The official prescribing information for angiotensin II notes that no specific studies have yet been conducted that examine the distribution of angiotensin II.
The official prescribing information notes that the clearnace of angiotensin II is not dependent on hepatic function or renal function.

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Metabolism / Metabolites
It is metabolized by aminopeptidase A and angiotensin converting enzyme 2 to angiotensin-(2-8) [angiotensin III] and angiotensin-(1-7), respectively in plasma, erythrocytes and many of the major organs (i.e. intestine, kidney, liver and lung). Angiotensin II type 1 receptor (AT1) mediated activity of angiotensin III is approximately 40% of angiotensin II; however, aldosterone synthesis activity is similar to angiotensin II. Angiotensin-(1-7) exerts the opposite effects of angiotensin II on AT1 receptors and causes vasodilation. Nevertheless, the official prescribing information also notes that no formal studies have been conducted that examine the metabolism of angiotensin II.

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Biological Half-Life
The plasma half-life of intravenously administered angiotensin II is less than one minute.

Toxicity Summary
The pharmacologic effect of this drug is to raise blood pressure. An overdose of the drug could result in hypertension. Careful monitoring and titration of the drug should prevent this effect, but in the even that it occurs, the short plasma half-life of angiotensin II means that this toxicity is easily reversible, and no antidote or further treatment should be required. The potential for thromboembolic events in patients treated with angiotensin II dictates the need for DVT prophylaxis during treatment.

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Adverse Effects
Most Common Adverse Events During Clinical Trials
* Thromboembolic events (12.9%) including DVT (4.3%)
* Thrombocytopenia (9.8%)
* Tachycardia (8.6%)

Other adverse reactions occurring at greater than 4%
* Fungal infection
* Delirium
* Acidosis
* Hyperglycemia
* Peripheral ischemia
The safety of the active drug was similar to placebo. Compared with placebo, fewer patients receiving angiotensin II required discontinuation of the drug due to serious adverse events. The rates of anticipated adverse events such as tachyarrhythmias, ventricular tachycardia, atrial tachycardia, and distal ischemia were similar between the two groups.

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172198 rat LD50 intravenous 17400 ug/kg Kiso to Rinsho. Clinical Report., 24(6079), 1990
172198 mouse LD50 intravenous 30800 ug/kg Kiso to Rinsho. Clinical Report., 24(6079), 1990

[1]. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000 Sep;52(3):415-72.

[2]. Role of angiotensin II in blood pressure regulation and in the pathophysiology of cardiovascular disorders. J Hum Hypertens. 1995 Nov;9 Suppl 5:S19-24.

[3]. Angiotensin II induces capillary formation from endothelial cells via the LOX-1 dependent redox-sensitive pathway. Hypertension. 2007;50(5):952-957.

[4]. Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines. Circulation. 2004;110(23):3581-3586.

[5]. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17985-90.

Pharmacodynamics
Angiotensin II is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone-system (RAAS) that has the capacity to cause vasoconstriction and an increase in blood pressure in the human body. In the RAAS, juxtaglomerular cells of the renal afferent arteriole synthesize the proteolytic enzyme renin. Although stored in an inactive form called pro-renin, decreases in arterial blood pressure or extracellular fluid volume depletion can cause various enzymatic reactions to release active renin into the systemic circulation and surrounding tissues. Such renin release allows for the production of the alpha-2-globulin angiotensinogen predominantly in the liver and to some extent, the kidneys and other organs. Angiotensin I, itself a decapeptide with weak biological activity, is produced from angiotensinogen and then quickly converted to angiotensin II by angiotensin converting enzymes (ACE). Consequently, angiotensin II demonstrates its strong vasopressor activity when it is rapidly degraded by aminopeptidases A and M into further entities like angiotensin III and angiotensin IV, respectively. Such species like angiotensin III can then bind and interact with specific G protein coupled receptors like angiotensin receptor 1, or AT-1 where strong vasoconstricson can occur. Furthermore, in the ATHOS-3 clinical trial, for the 114 (70%) patient subjects in the angiotensin II arm who reached the target mean arterial pressure (MAP) at Hour 3, the median time to reach the target MAP endpoint was approximately 5 minutes. The angiotensin II was titrated to effect for each individual patient.

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Ile(5)-angiotensin II is an angiotensin II that acts on the central nervous system (PDB entry: 1N9V). It has a role as a human metabolite. It is a tautomer of an Ile(5)-angiotensin II dizwitterion.
Angiotensin II is under investigation for the treatment of Sepsis, Septic Shock, Diabetes Mellitus, and Acute Renal Failure. Angiotensin II has been investigated for the treatment, basic science, and diagnostic of Hypertension, Renin Angiotensin System, and Idiopathic Membranous Nephropathy. As of December 21, 2017 the FDA approved La Jolla Pharmaceutical's Giapreza (angiotensin II) Injection for Intravenouse Infusion for the indication of acting as a vasoconstrictor to increase blood pressure in adults with septic or other distributive shock. The novelty of the medication lies in the fact that it is the first and only use of synthetic human angiotensin II to help maintain body blood pressure. Shock is the inability to maintain blood flow to vital tissues and the potential resultant organ failure and death within hours, no matter young or o ld. As distributive shock is the most common type of shock in the inpatient setting and affects up to one third of patients in the intensive care unit, the FDA determined that there is a need for treatment options for critically ill hypotensive patients who do not adequately respond to currently available therapies.

Angiotensin ii is a Vasoconstrictor. The physiologic effect of angiotensin ii is by means of Vasoconstriction.
Therapeutic Angiotensin II is a synthetic form of the endogenous angiotensin II, a peptide hormone of the renin-angiotensin-aldosterone system (RAAS) that causes vasoconstriction and an increase in blood pressure, that may be used for the treatment of septic or other distributive shock. Upon administration, therapeutic angiotensin II binds to angiotensin II type 1 receptor on vascular smooth muscle cells which leads to Ca2+/calmodulin-dependent phosphorylation of myosin. This causes smooth muscle contraction and results in vasoconstriction and an increase in blood pressure. Therapeutic angiotensin II also increases blood pressure by stimulating the release of the steroid hormone aldosterone, which regulates the renal absorption of water and sodium.

ANGIOTENSIN II is a Protein drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 2017 and has 4 approved and 4 investigational indications.
An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.

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Drug Indication
Angiotensin II is a vasoconstrictor indicated for increasing blood pressure in adults with septic or other distributive shock.
Giapreza is indicated for the treatment of refractory hypotension in adults with septic or other distributive shock who remain hypotensive despite adequate volume restitution and application of catecholamines and other available vasopressor therapies.

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We postulated that Ang II may enhance VEGF expression and capillary formation via LOX-1 upregulation. Indeed, our study demonstrates that this is the case. In 2 different models of capillary tube formation, we showed that the anti–LOX-1 antibody suppressed the angiogenic response to Ang II. This was not an incidental finding, because nonspecific IgG did not have a similar effect. Studies with the use of aortic rings from the LOX-1 null mouse revealed a minimal angiogenic response to Ang II. Both losartan and apocynin blocked Ang II–mediated LOX-1 expression, as well as capillary tube formation. It is noteworthy that the activation of MAPKs was found to be downstream of LOX-1 expression, because the inhibitors of MAPKs did not influence the expression of LOX-1, yet they inhibited capillary tube formation. Perspectives This study demonstrates the potent angiogenic response to Ang II, which is mediated in large part by the induction of LOX-1 via AT1R and the generation of ROS. We have shown recently the significance of LOX-1 in LDL receptor/LOX-1 double-null mice that are resistant to atherogenesis despite the feeding of an atherogenic diet.7 The current study further suggests that LOX-1 may be a reasonable target of antiatherogenesis therapy.[3]

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In conclusion, in this study we have demonstrated that Ang II induces neutrophil accumulation in vivo via the secretion of CXC chemokines, the source of which may include endothelial cell Weibel-Palade bodies and vascular smooth muscle cells, and this effect is mediated through interaction of Ang II with its AT1 receptor. Ang II is formed from the decapeptide Ang I by the action of a carboxydipeptidase, angiotensin-converting enzyme, found on the endothelial cell surface and in the plasma. An alternative source of Ang II generation in the heart is mast cell chymase, which generates Ang II directly from Ang I. Therefore, Ang II should be considered a potential inflammatory mediator of neutrophil infiltration observed in acute myocardial infarction through the release of CXC chemokines, and CXC receptor antagonists may become a powerful tool in the control of inflammation associated with acute myocardial infarction.[4]

C52H72F3N13O14

1160.20200252533

1159.527

C, 53.83; H, 6.26; F, 4.91; N, 15.69; O, 19.31

2761969-44-0

Angiotensin II human;4474-91-3;Angiotensin II human acetate;68521-88-0;Angiotensin II human-13C6,15N TFA

146047991

H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-OH.TFA; Asp-Arg-Val-Tyr-Ile-His-Pro-Phe; L-alpha-aspartyl-L-arginyl-L-valyl-L-tyrosyl-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine trifluoroacetic acid

DRVYIHPF

White to off-white solid powder

14

20

29

82

2060

9

C(F)(F)(F)C(=O)O.C(N1CCC[C@H]1C(=O)N[C@H](C(=O)O)CC1C=CC=CC=1)(=O)[C@@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC(=O)O)CC1C=CC(O)=CC=1)CC1NC=NC=1

FYMJZKAYBCZPKL-PIONDTTLSA-N

InChI=1S/C50H71N13O12.C2HF3O2/c1-5-28(4)41(47(72)59-36(23-31-25-54-26-56-31)48(73)63-20-10-14-38(63)45(70)60-37(49(74)75)22-29-11-7-6-8-12-29)62-44(69)35(21-30-15-17-32(64)18-16-30)58-46(71)40(27(2)3)61-43(68)34(13-9-19-55-50(52)53)57-42(67)33(51)24-39(65)66;3-2(4,5)1(6)7/h6-8,11-12,15-18,25-28,33-38,40-41,64H,5,9-10,13-14,19-24,51H2,1-4H3,(H,54,56)(H,57,67)(H,58,71)(H,59,72)(H,60,70)(H,61,68)(H,62,69)(H,65,66)(H,74,75)(H4,52,53,55);(H,6,7)/t28-,33-,34-,35-,36-,37-,38-,40-,41-;/m0./s1

(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxy-2-phenylethyl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid;2,2,2-trifluoroacetic acid

Angiotensin II human TFA; Angiotensin II human (TFA); 2761969-44-0; CHEMBL4303682; Angiotensin II TFA;Ang II TFA;DRVYIHPF TFA;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : 10 mg/mL (8.62 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)