Angiotensin II
(Synonyms: 血管紧张素II,Asp-Arg-Val-Tyr-Ile-His-Pro-Phe ) 目录号 : GP10023
血管紧张素II是肾素/血管紧张素系统的主要生物活性肽和一种血管收缩剂。
Cas No.:4474-91-3
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
|
Cell lines |
HCAEC cells |
|
Preparation Method |
HCAECs were exposed to Angiotensin II (0, 0.1, 1, 5, 10, 20, 50, and 100 nmol/L) for 24 hours. |
|
Reaction Conditions |
Angiotensin II (0, 0.1, 1, 5, 10, 20, 50, and 100 nmol/L) for 24 hours |
|
Applications |
Angiotensin II (1 nM) induces the expression of LOX-1 and VEGF and enhances capillary formation from human coronary endothelial cells in Matrigel assay. Angiotensin 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, are suppressed by anti-LOX-1 antibody, nicotinamide-adenine dinucleotide phosphate oxidase inhibitor apocynin and the Angiotensin II type 1 receptor blocker Losartan, but not by the Ang II type 2 receptor blocker PD123319. |
| Animal experiment [2]: | |
|
Animal models |
(129 × C57BL/6) F1 mice lacking AT1A receptors |
|
Preparation Method |
To distinguish the AT1 receptor population that is critical for the pathogenesis of hypertension, osmotic minipumps were implanted s.c. into each animal to infuse Angiotensin II (1,000 ng/kg/min) continuously for 4 weeks. |
|
Dosage form |
Angiotensin II (1,000 ng/kg/min) for 4 weeks. |
|
Applications |
AT1 receptors in the kidney are primarily responsible for the actions of Angiotensin II to cause hypertension. |
|
References: [1]: Hu C, Dandapat A, et,al. Angiotensin II induces capillary formation from endothelial cells via the LOX-1 dependent redox-sensitive pathway. Hypertension. 2007 Nov;50(5):952-7. doi: 10.1161/HYPERTENSIONAHA.107.096446. Epub 2007 Sep 24. PMID: 17893372. |
|
Angiotensin II is a vasoconstrictor and the main bioactive peptide of the renin/Angiotensin system. Angiotensin II human plays a central role in the regulation of 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 (AT2R) interact to mediate[1].
Human induces capillary formation in endothelial cells through a LOX-1-dependent redox-sensitive pathway. Angiotensin II (1 nM) induces the expression of LOX-1 and VEGF and enhances capillary formation from human coronary endothelial cells in Matrigel assay[3,4].Angiotensin II helps to regulate overall renal tubular reabsorption of salt and water, Angiotensin II directly stimulates epithelial sodium channel activity through an AT1 receptor-dependent mechanism[8].Angiotensin II Human induces the growth of vascular smooth muscle cells, increases the synthesis of collagen type I and III in fibroblasts, leads to the thickening of the vascular wall and myocardium, and induces fibrosis. Angiotensin II also induces apoptosis[2].The effects of Angiotensin II to increase blood pressure are mediated by AT1 receptors[1], and these receptors are expressed in a variety of organ systems thought to play key roles in blood pressure homeostasis, including the heart, kidney, blood vessels, adrenal glands, and cardiovascular control centers in the brain[5]. In the brain, intraventricular injection of Angiotensin II causes a dramatic pressor response that is mediated by AT1A receptors[6].
In mice, AT1 receptors in the kidney are primarily responsible for the actions of Angiotensin II to cause hypertension[7]. Angiotensin II induction of NETosis in vitro via ROS/ peptidyl arginine deiminase type 4 and autophagy dependent pathways In EH patients initiated with Angiotensin II receptor blockers, circulating NETs and thrombin production levels were significantly reduced, whereas their plasma was unable to trigger procoagulant NETs [9].
References:
[1]: de Gasparo M, Catt KJ, et,al. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000 Sep;52(3):415-72. PMID: 10977869.
[2]: Fyhrquist F, Mets?rinne K, et,al. 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. PMID: 8583476.
[3]: Hu C, Dandapat A, et,al. Angiotensin II induces capillary formation from endothelial cells via the LOX-1 dependent redox-sensitive pathway. Hypertension. 2007 Nov;50(5):952-7. doi: 10.1161/HYPERTENSIONAHA.107.096446. Epub 2007 Sep 24. PMID: 17893372.
[4]: Nabah YN, Mateo T, et,al. Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines. Circulation. 2004 Dec 7;110(23):3581-6. doi: 10.1161/01.CIR.0000148824.93600.F3. Epub 2004 Nov 29. PMID: 15569833.
[5]: Shanmugam S, Sandberg K. Ontogeny of angiotensin II receptors. Cell Biol Int. 1996 Mar;20(3):169-76. doi: 10.1006/cbir.1996.0021. PMID: 8673065.
[6]: Davisson RL, Oliverio MI, et,al. Divergent functions of angiotensin II receptor isoforms in the brain. J Clin Invest. 2000 Jul;106(1):103-6. doi: 10.1172/JCI10022. PMID: 10880053; PMCID: PMC314366.
[7]: Crowley SD, Gurley SB, et,al. 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. doi: 10.1073/pnas.0605545103. Epub 2006 Nov 7. PMID: 17090678; PMCID: PMC1693859.
[8]: Peti-Peterdi J, Warnock DG, et,al. Angiotensin II directly stimulates ENaC activity in the cortical collecting duct via AT(1) receptors. J Am Soc Nephrol. 2002 May;13(5):1131-5. doi: 10.1097/01.asn.0000013292.78621.fd. PMID: 11960999.
[9]: Chrysanthopoulou A, Gkaliagkousi E, et,al. Angiotensin II triggers release of neutrophil extracellular traps, linking thromboinflammation with essential hypertension. JCI Insight. 2021 Sep 22;6(18):e148668. doi: 10.1172/jci.insight.148668. PMID: 34324440; PMCID: PMC8492353.
血管紧张素II是肾素/血管紧张素系统的主要生物活性肽和一种血管收缩剂。在人体内，血管紧张素II通过与G蛋白偶联受体（GPCR）—— 血管紧张素II类型1受体（AT1R）和血管紧张素II类型2受体（AT2R）相互作用来调节人类的血压，其中AT1R和AT2R起到中心作用[1]。
人体通过一种LOX-1依赖的氧化还原敏感途径诱导内皮细胞形成毛细血管。肾素-血管紧张素系统中的肾素酶会将肾素转化为血管紧张素I，而后者再被转化为血管紧张素II（浓度为1纳摩尔）。这个过程会引起LOX-1和VEGF表达增加，并促进人类冠状动脉内皮细胞在Matrigel试验中形成毛细血管[3,4]。此外，肾上腺髓质分泌的去甲肾上腺素也能刺激AT1受体，从而使得心率、收缩压和舒张压升高。
同时，肾上腺髓质分泌的去甲肾上腺素也可以直接作用于远端小球旁通道及近曲小管等部位，在调节整体盐水重吸收方面发挥作用。Angiotensin II还能够诱导平滑肌细胞生长、增加成纤维细胞合成Ⅰ型和Ⅲ型胶原，并导致血管壁和心室壁变厚以及引起纤维化反应。此外，Angiotensin II还能够诱导细胞凋亡[2]。
肾素-血管紧张素系统通过AT1受体介导增加血压的效应在多个器官系统中发挥作用，这些器官被认为在血压稳态调节中起着关键作用，包括心脏、肾脏、血管、肾上腺和控制心血管的大脑区域[5]。在大脑中，注射Angiotensin II到侧脑室会引起剧烈的升压反应，并且这种反应是由AT1A受体介导的[6]。
在小鼠中，肾脏中的AT1受体主要负责血管紧张素II引起高血压的作用。通过ROS/ peptidyl arginine deiminase type 4和自噬依赖途径，在体外诱导Angiotensin II NETosis。在使用Angiotensin II受体拮抗剂开始治疗的EH患者中，循环NETs和凝血酶产生水平显着降低，而它们的血浆无法触发促凝状态的NETs。
| Cas No. | 4474-91-3 | SDF | |
| 别名 | 血管紧张素II,Asp-Arg-Val-Tyr-Ile-His-Pro-Phe | ||
| 化学名 | Angiotensin II | ||
| Canonical SMILES | CCC(C)C(C(=O)NC(CC1=CN=CN1)C(=O)N2CCCC2C(=O)NC(CC3=CC=CC=C3)C(=O)O)NC(=O)C(CC4=CC=C(C=C4)O)NC(=O)C(C(C)C)NC(=O)C(CCCN=C(N)N)NC(=O)C(CC(=O)O)N.CC(=O)O | ||
| 分子式 | C50H71N13O12 | 分子量 | 1046.2 |
| 溶解度 | ≥ 100.2mg/mL in Water | 储存条件 | Store at -20°C, protect from light, stored under nitrogen |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 0.9558 mL | 4.7792 mL | 9.5584 mL |
| 5 mM | 0.1912 mL | 0.9558 mL | 1.9117 mL |
| 10 mM | 0.0956 mL | 0.4779 mL | 0.9558 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Angiotensin II revisited: new roles in inflammation, immunology and aging
That the renin-angiotensin system (RAS) is involved in regulation of blood pressure, vasoconstriction, sodium intake and potassium excretion is well established. Studies in the last few years have however documented new roles for this molecule as a pro-inflammatory molecule and more recently as a possible pro-fibrotic agent that contributes to progressive deterioration of organ function in disease. Binding of Ang II to its receptors (in particular AT(1)) mediates intracellular free radical generation that contributes to tissue damage by promoting mitochondrial dysfunction. Blocking Ang II signalling protects against neurodegenerative processes and promotes longevity in rodents. Altogether these findings open the unanticipated perspective for exploring Ang II signalling in therapeutic interventions in inflammatory diseases and aging-related tissue injury. This review extends from the discovery of Ang II and its implications in renal and cardiovascular physiology to cover the roles of the system in inflammation, tissue injury, autoimmunity, oxidative stress and aging.
Update on Angiotensin II Subtype 2 Receptor: Focus on Peptide and Nonpeptide Agonists
Angiotensin II (Ang II) is the most dominant effector component of the renin-angiotensin system (RAS) that generally acts through binding to two main classes of G protein-coupled receptors, namely Ang II subtype 1 receptor (AT1R) and angiotensin II subtype 2 receptor (AT2R). Despite some controversial reports, the activation of AT2R generally antagonizes the effects of Ang II binding on AT1R. Studying AT2R signaling, function, and its specific ligands in cell culture or animal studies has confirmed its beneficial effects throughout the body. These characteristics classify AT2R as part of the protective arm of the RAS that, along with functions of Ang (1-7) through Mas receptor signaling, modulates the harmful effects of Ang II on AT1R in the activated classic arm of the RAS. Although Ang II is the primary ligand for AT2R, we have summarized other natural or synthetic peptide and nonpeptide agonists with critical evaluation of their structure, mechanism of action, and biologic activity. SIGNIFICANCE STATEMENT: AT2R is one of the main components of the RAS and has a significant prospective for mediating the beneficial action of the RAS through its protective arm on the body's homeostasis. Targeting AT2R offers substantial clinical application possibilities for modulating various pathological conditions. This review provided concise information regarding the AT2R peptide and nonpeptide agonists and their potential clinical applications for various diseases.
Angiotensin II in type 2 diabetes mellitus
Angiotensin II (Ang II) is well-known as a systemic vasoconstrictor but recently a novel role for the peptide in endocrine function has been suggested and it has been linked to the pathophysiology of type 2 diabetes mellitus. According to several large-scale clinical studies, blocking Ang II prevented the onset of type 2 diabetes in potential patients. Type 2 diabetes is a complicated disease that is primarily characterized by insulin resistance and relative insulin deficiency mediated by numerous organs. Among these organs, the pancreas, adipose tissue, skeletal muscle and liver are the most prominent in maintaining glucose homeostasis. Interestingly, locally generated Ang II has been identified in these organs, where it plays different physiological roles and is produced in relatively high amounts with significant function. In type 2 diabetic human patients or animal models, Ang II, its generating enzymes and receptors are up-regulated and trigger detrimental effects. Moreover, Ang II seems to play roles in the regulation of insulin secretion by the pancreatic beta-cell and insulin sensitivity by peripheral tissues, which are two critical factors contributing to the development of type 2 diabetes. Accordingly, inhibiting Ang II produced beneficial effects on individual organs and throughout the body. Therefore, the present review discusses the role of Ang II in particular organs during normal physiological conditions as well as in type 2 diabetes.
Angiotensin II, angiotensin II antagonists and spironolactone and their modulation of cardiac repolarization
Angiotensin II and aldosterone produce pro-arrhythmic effects by several mechanisms, including the modulation of voltage-dependent K(+) channels involved in human cardiac repolarization. Drugs that inhibit the renin-angiotensin-aldosterone system exert anti-arrhythmic actions that are related to the blockade of the pro-arrhythmic actions of angiotensin II and aldosterone. These anti-arrhythmic actions include inhibition of electrical and structural cardiac remodeling, inhibition of neurohumoral activation, reduction of blood pressure and stabilization of electrolyte disturbances. In this article, several angiotensin II AT(1) receptor antagonists (candesartan, E3174, eprosartan, irbesartan and losartan) and aldosterone receptor antagonists (canrenoic acid and spironolactone) that directly modulate the activity of the voltage-dependent K(+) channels are reviewed; the effects of these antagonists might be useful in the prevention and treatment of cardiac arrhythmias.
The angiotensin II receptor and the actions of angiotensin II
Angiotensin II (Ang II) is a potent effector peptide of the renin-angiotensin system that exerts a wide variety of physiological actions on the cardiovascular, renal, endocrine, and central and peripheral nervous systems. Angiotensin exerts its actions by binding to specific receptors in the plasma membrane of various tissues. Structure-activity relationship studies and competition-binding experiments have identified a potency series of angiotensin analogues. Such studies have demonstrated that target organs display different preferences for Ang II and homologues such as Ang III and des-[Phe8] angiotensin II. Similarly, agents that normally are considered to be pure receptor antagonists for a given response (tissue) are full agonists in other tissues. Indirect evidence obtained from the above studies have led to the speculation that there are multiple angiotensin receptor subtypes among various tissues as well as within single cell types. Multiple mechanisms of signal transduction have been demonstrated for angiotensin. For example, depending on the effector organ, angiotensin stimulates phosphoinositide turnover and release of internal calcium, modulates voltage-dependent calcium channels, directly activates calcium channels, and inhibits adenylate cyclase activity. Recently, the identification of selective, high-affinity peptide and nonpeptide antagonists has resulted in further characterization of angiotensin receptors into distinct subtypes. In addition, dithiothreitol, an agent that reduces disulfide bridges, has been a useful tool in the characterization of angiotensin receptors as the subtypes apparently are not affected equally by this agent. However, further work needs to be performed to characterize angiotensin receptors with respect to heterogeneity, structure, transducing mechanisms, and physiological function.