Angiotensin II human (Angiotensin II) acetate is a vasoconstrictor and the major biologically active peptide of the renin/angiotensin system. Angiotensin II human acetate plays a central role in regulating human blood pressure, mainly through angiotensin II and G protein-coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor. mediated by interactions between AT2Rs. Angiotensin II human acetate stimulates sympathetic stimulation, increases aldosterone biosynthesis and renal activity. Angiotensin II human acetate induces the growth of vascular smooth muscle cells and increases the synthesis of type I and type III collagen in fibroblasts, leading to thickening of vessel walls and myocardium, and leading to fibrosis. Angiotensin II human acetate also causes apoptosis. Angiotensin II human acetate induces capillary formation in endothelial cells via a LOX-1-dependent redox-sensitive pathway.

Physicochemical Properties

Molecular Formula	C52H75N13O14
Molecular Weight	1106.23
Exact Mass	1105.56
CAS #	68521-88-0
Related CAS #	Angiotensin II human;4474-91-3;Angiotensin II human TFA;2761969-44-0
PubChem CID	172197
Appearance	White to off-white solid powder
LogP	3.16
Hydrogen Bond Donor Count	14
Hydrogen Bond Acceptor Count	17
Rotatable Bond Count	29
Heavy Atom Count	79
Complexity	2010
Defined Atom Stereocenter Count	9
SMILES	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.CC(=O)O
InChi Key	VBTZKFAHKJXHBA-PIONDTTLSA-N
InChi Code	InChI=1S/C50H71N13O12.C2H4O2/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;1-2(3)4/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);1H3,(H,3,4)/t28-,33-,34-,35-,36-,37-,38-,40-,41-;/m0./s1
Chemical Name	acetic acid;(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
HS Tariff Code	2934.99.9001
Storage	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.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	AT1 Receptor AT2 Receptor
ln Vitro	Angiotensin II (Ang II) human acetate's majority of known effects are mediated by AT1 receptors, whereas the AT2 receptor helps control blood pressure and kidney function[1]. Vasoconstriction, sympathetic nervous system stimulation, enhanced aldosterone production, and renal activities are the main ways that angiotensin II human acetate elevates blood pressure (BP). Additional effects of Angiotensin II human acetate include stimulating the development, migration, and mitosis of vascular smooth muscle cells; fibroblasts producing more collagen type I and III, which thickens the heart and vascular wall; and fibrosis. Type 1 Ang II receptors (AT1) mediate these actions[2]. In the Matrigel experiment, angiotensin II (1 nM) increases capillary formation from human coronary endothelial cells and stimulates the production of LOX-1 and VEGF. The Ang II type 1 receptor blocker Losartan, the nicotinamide-adenine dinucleotide phosphate oxidase inhibitor apocynin, and the anti-LOX-1 antibody all inhibited the effects of angiotensin II-mediated expression of VEGF and LOX-1, capillary formation, intracellular reactive oxygen species generation, and phosphorylation of p38 and p44/42 mitogen-activated protein kinases[3]. However, the Ang II type 2 receptor blocker PD123319 did not have this effect.
ln Vivo	Angiotensin II human (5 mL of 1 nM; intraperitoneal injection; 200–250 g Sprague-Dawley rats) acetate causes a notable increase in neutrophil recruitment, which peaked at 4 hours and resolved by 24[4]. Each rat has an osmotic minipumps implanted subcutaneously to continuously inject Angiotensin II human (1000 ng/kg/min) acetate for four weeks in order to identify the AT1 receptor population that is crucial for the etiology of hypertension. By stimulating AT1 receptors in the kidney and facilitating salt reabsorption, angiotensin II human acetate raises blood pressure[5].
References	[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.
Additional Infomation	See also: Angiotensin II Acetate (annotation moved to). Drug Indication 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.

Solubility Data

Solubility (In Vitro)

H2O : 25 mg/mL (22.60 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 10 mg/mL (9.04 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. Solubility in Formulation 2: 16.67 mg/mL (15.07 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.9040 mL	4.5199 mL	9.0397 mL
	5 mM	0.1808 mL	0.9040 mL	1.8079 mL
	10 mM	0.0904 mL	0.4520 mL	0.9040 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.