Angiotensin II type 1 receptor (AT1R); Angiotensin II type 2 receptor (AT2R)

The AT1 receptor, which helps control blood pressure and kidney function, mediates the majority of the actions of angiotensin II (Ang II) in humans [1]. Vasoconstriction, sympathetic stimulation, enhanced aldosterone production, and renal effects are the main actions of angiotensin II on humans that raise blood pressure (BP). Human angiotensin II also causes vascular smooth muscle cells to proliferate, migrate, and undergo mitosis. It also causes fibroblasts to produce more type I and type III collagen-producing proteins, which thickens blood vessel walls and myocardium and causes fibrosis. Ang II type 1 (AT1) mediates these effects[2]. In Matrigel tests, angiotensin II human (1 nM) increases capillary development in human coronary endothelial cells and stimulates LOX-1 and VEGF. LOX-1 and VEGF expression, capillary formation, and intracellular reactive oxygen species production are mediated by antibodies to nicotinamide adenylate inhibitor and angiotensin II human. Phosphate oxidase conjugates apocynin and the Ang II type 1 receptor blocker losartan, but not the Ang II type 2 receptor blocker PD123319 [3].

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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].

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

Absorption, Distribution and Excretion
In adult patients with sepsis or other distributive shock, serum angiotensin II levels were similar at baseline and 3 hours after intravenous infusion. Serum angiotensin I (the precursor peptide of angiotensin II) levels decreased by approximately 40% 3 hours after treatment. Official prescribing information indicates that there are currently no specific studies on angiotensin II clearance. Official prescribing information indicates that there are currently no specific studies on angiotensin II distribution. Official prescribing information indicates that angiotensin II clearance is independent of liver or kidney function. Metabolism/Metabolites In plasma, erythrocytes, and many major organs (such as the intestine, kidney, liver, and lung), angiotensin II is metabolized by aminopeptidase A and angiotensin-converting enzyme 2 to angiotensin-(2-8) [angiotensin III] and angiotensin-(1-7], respectively. Angiotensin III's activity mediated by the angiotensin II type 1 receptor (AT1) is approximately 40% that of angiotensin II; however, its aldosterone synthesis activity is similar to that of angiotensin II. Angiotensin-(1-7) acts on the AT1 receptor in the opposite way to angiotensin II, causing vasodilation. Nevertheless, official prescribing information also indicates that no formal studies have been conducted to investigate the metabolism of angiotensin II.

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Biological Half-Life
The plasma half-life of intravenously injected angiotensin II is less than 1 minute.

Toxicity Overview
The pharmacological action of this drug is to raise blood pressure. Overdose may lead to hypertension. This adverse reaction can be prevented by close monitoring and dosage adjustment, but even if it occurs, the toxicity is easily reversed due to the short plasma half-life of angiotensin II, usually without the need for an antidote or further treatment. Patients receiving angiotensin II are at risk of thromboembolic events, therefore deep vein thrombosis prophylaxis is required during treatment.

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Adverse Reactions
Most common adverse events in clinical trials
Thromboembolic events (12.9%), including deep vein thrombosis (4.3%)
Thrombocytopenia (9.8%)
Tachycardia (8.6%)
Other adverse reactions with an incidence greater than 4%
Fungal infection
Delirium
Acidosis
Hyperglycemia
Peripheral ischemia
The safety profile of the active drug is similar to that of placebo. Compared with placebo, fewer patients receiving angiotensin II treatment required discontinuation due to serious adverse events. The incidence of expected adverse events (such as tachyarrhythmias, ventricular tachycardia, atrial tachycardia, and distal ischemia) was similar in both groups.

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172198 Rat intravenous LD50 17400 ug/kg, Kiso to Rinsho. Clinical Report., 24(6079), 1990
172198 Mouse intravenous LD50 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 in the renin-angiotensin-aldosterone system (RAAS) that causes vasoconstriction and raises blood pressure. In the RAAS, juxtaglomerular cells in the afferent arterioles of the kidney synthesize the proteolytic enzyme renin. Although renin is stored in an inactive form called reninogen, a decrease in arterial blood pressure or extracellular fluid volume can trigger various enzymatic reactions that release active renin into the systemic circulation and peripheral tissues. This renin release results in the primary production of α2-globulin angiotensinogen in the liver, with smaller amounts produced in the kidneys and other organs. Angiotensin I itself is a relatively inactive decapeptide, produced from angiotensinogen and then rapidly converted to angiotensin II by angiotensin-converting enzyme (ACE). Therefore, angiotensin II exhibits potent vasopressor activity when rapidly degraded by aminopeptidases A and M into other substances such as angiotensin III and angiotensin IV. Angiotensin III and other substances can bind to and interact with specific G protein-coupled receptors (such as angiotensin receptor 1, AT-1), resulting in strong vasoconstriction. Furthermore, in the ATHOS-3 clinical trial, 114 (70%) patients in the angiotensin II group reached their target mean arterial pressure (MAP) at 3 hours, with a median time to reach the target MAP endpoint of approximately 5 minutes. Angiotensin II dosage is titrated based on individual patient circumstances. Ile(5)-angiotensin II is a centrally acting angiotensin II (PDB accession number: 1N9V). It is a human metabolite. It is a zwitterion of Ile(5)-angiotensin II. Angiotensin II is being investigated for the treatment of sepsis, septic shock, diabetes, and acute renal failure. Angiotensin II has been investigated for therapeutic, basic scientific research, and diagnostic purposes in hypertension, the renin-angiotensin system, and idiopathic membranous nephropathy. As of December 21, 2017, the FDA approved La Jolla Pharmaceuticals' Giapreza (angiotensin II) injection for intravenous infusion as a vasoconstrictor to raise blood pressure in adult patients with septic shock or other distributive shock. The drug's innovation lies in being the first and currently only medication to use synthetic human angiotensin II to help maintain blood pressure. Shock is the inability to maintain blood supply to vital tissues, potentially leading to organ failure and death, and can occur within hours regardless of age. Because distributive shock is the most common type of shock in hospitalized patients, affecting up to one-third of patients in intensive care units, the FDA determined that new treatment options were needed for critically ill patients with hypotension who did not respond well to existing therapies. Angiotensin II is a vasoconstrictor. The physiological effect of angiotensin II is achieved through vasoconstriction. Therapeutic angiotensin II is the synthetic form of endogenous angiotensin II, a peptide hormone of the renin-angiotensin-aldosterone system (RAAS) that causes vasoconstriction and increased blood pressure. It is used to treat septic shock or other distributive shock. After administration, therapeutic angiotensin II binds to angiotensin II type 1 receptors on vascular smooth muscle cells, leading to calcium/calmodulin-dependent phosphorylation of myosin. This causes smooth muscle contraction, resulting in vasoconstriction and increased blood pressure. Therapeutic angiotensin II also raises blood pressure by stimulating the release of the steroid hormone aldosterone, which regulates the reabsorption of water and sodium by the kidneys. Angiotensin II is a protein drug, with clinical trials up to Phase IV (covering all indications). It was first approved in 2017 and currently has four approved indications and four investigational indications. It is a potent but unstable octapeptide vasoconstrictor. It is produced by removing two amino acids from the IC terminus of angiotensin II using angiotensin-converting enzyme. The fifth amino acid varies among different species. To block the vasoconstrictive and hypertensive effects of angiotensin II, patients are usually treated with ACE inhibitors or angiotensin II type 1 receptor blockers.

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Drug Indications
Angiotensin II is a vasoconstrictor indicated for the treatment of adult sepsis or other distributive shock to raise blood pressure.
Gipreza is indicated for the treatment of adult sepsis or other distributive shock with refractory hypotension despite adequate volume resuscitation and the use of catecholamines and other available vasopressors.
We hypothesized that angiotensin II might enhance VEGF expression and capillary formation by upregulating LOX-1. Indeed, our study confirms this. In two different capillary formation models, we found that anti-LOX-1 antibodies inhibited the angiotensin II angiogenic response. This was not accidental, as nonspecific IgG did not have a similar effect. Studies using the aortic rings of LOX-1 knockout mice have shown that angiotensin II (Ang II)-induced angiogenesis is extremely weak. Both losartan and apoxitin can block Ang II-mediated LOX-1 expression and capillary tubular formation. Notably, MAPK activation is downstream of LOX-1 expression, as MAPK inhibitors do not affect LOX-1 expression but do inhibit capillary tubular formation. Outlook: This study reveals a potent Ang II-induced angiogenesis response primarily mediated by AT1R-mediated LOX-1 expression and reactive oxygen species (ROS) generation. We recently demonstrated the importance of LOX-1 in LDL receptor/LOX-1 double knockout mice, which resist atherosclerosis even when fed an atherosclerotic diet. This study further suggests that LOX-1 may be a plausible therapeutic target for anti-atherosclerosis. [3] In summary, this study suggests that angiotensin II (Ang II) induces neutrophil aggregation in vivo by secreting CXC chemokines, which may originate from endothelial Weibel-Palade bodies and vascular smooth muscle cells, and this effect is mediated by the interaction of Ang II with its AT1 receptor. Ang II is generated from decapeptide Ang I under the action of carboxydipeptidase (angiotensin-converting enzyme), which is present on the surface of endothelial cells and in plasma. Another source of Ang II generation in the heart is mast cell chymotrypsin, which can directly generate Ang II from Ang I. Therefore, Ang II should be considered a potential inflammatory mediator of neutrophil infiltration observed in acute myocardial infarction, which exerts its effects by releasing CXC chemokines, and CXC receptor antagonists may be a powerful tool for controlling acute myocardial infarction-related inflammation. [4]

C50H71N13O12

1046.1787

1045.534

C, 57.40; H, 6.84; N, 17.41; O, 18.35

4474-91-3

Talfirastide;51833-78-4;Angiotensin II human acetate;68521-88-0;Angiotensin II human TFA;2761969-44-0;Biotin-Ahx-Angiotensin II human;Angiotensin II human, FAM-labeled

172198

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

DRVYIHPF

White to off-white solid powder

1.4±0.1 g/cm3

809.08°C (rough estimate)

1.664

2.34

13

15

29

75

1980

9

CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)O)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N

CZGUSIXMZVURDU-JZXHSEFVSA-N

InChI=1S/C50H71N13O12/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/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)/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

ANGIOTENSIN II; Human angiotensin II; Angiotensin II (human); Ang II; 5-L-Isoleucineangiotensin II; 5-Isoleucine-angiotensin II; Angiotensin II (mouse); ...; 32044-01-2, 4474-91-3 (salt);

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)

DMSO : ~100 mg/mL (~95.59 mM)
H2O : ~50 mg/mL (~47.79 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (2.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: ≥ 0.83 mg/mL (0.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 4: 2 mg/mL (1.91 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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