Angiotensin (1-7)
(Synonyms: Asp-Arg-Val-Tyr-Ile-His-Pro ) 目录号 : GP10077
血管紧张素 1-7 (Ang-(1-7)) 是来自肾素-血管紧张素系统 (RAS) 的内源性七肽，由于其在心脏细胞中的抗炎和抗纤维化活性而具有心脏保护作用。
Cas No.:51833-78-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
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Kinase experiment: |
Competition assays using purified canine ACE are determined using a fixed concentration of the substrate Hip-His-Leu (1 mM) and varying the concentrations of the competing agents [Lisinopril (0.1 to 100 nM), Angiotensin (1-7) (10 nM to 10 μM), or Sar1, Thr8-Ang II (10 nM to 10 μM)]. Inhibitory constants (IC50) are determined from the respective competition curves. To study the effect of Angiotensin (1-7) on BK metabolism in intact coronary rings, 125I-[Tyr0]-BK (final concentration of 1 nM) is added to the tubes containing three rings preincubated with 1 mL Krebs' buffer and aerated with 95% O2 and 5% CO2 at 37°C. Lisinopril (2 μM), Angiotensin (1-7) (2 μM), or Krebs' buffer as control are added to the rings 10 minutes before addition of the radiolabeled BK. Aliquots of the incubation medium are removed at 5, 10, and 20 minutes and diluted with 1% HFBA to inhibit peptidase activity[1]. |
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Cell experiment: |
500 μM Methylglyoxal is incubated with 100 μM BSA dissolved in phosphate buffered saline (PBS) for 24 hours, then washed on 10 kDa filters to remove excess methyl glyoxal, reconstituted with DMEM/F12 serum free media and passed through a 0.2 μmicron filter. TGF-β (5 ng/mL) is prepared to treat cells in a subset of experiments. Cells are co-treated with one or combinations of the following: Angiotensin (1-7) (100 nM), D-Ala7-Ang-(1-7) (10 μM), ERK1/2 kinase inhibitor, PD 98059 (1 μM), TGF-β receptor kinase inhibitor; SB525334 (1 μM), the AT1 receptor antagonist Losartan (1 μM), the renin inhibitor Aliskerin (1 μM) and the ACE inhibitor Lisinopril (1 μM)[2]. |
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Animal experiment: |
Mice[3] Male and female BALB/c mice (1:1 ratio, 6-10 weeks old, mean weight 20 g.) are used. Angiotensin fragment 1-7 acetate salt hydrate (Ang 1-7) is dissolved in 0.9% saline (vehicle) at 1 mg/mL and stored at -80°C. Various doses (0.01, 0.06, 0.1, 0.3 and 1 mg/kg) are freshly prepared from the stock each day of the experiment, and administered to mice by daily intra-peritoneal (i.p) injections in a volume of 500 μL per injection, either before (prophylactic approach) or after (treatment approach) DSS treatment. A779 (MAS-1 R antagonist) is similarly dissolved in distilled water at 1 mg/mL and stored at -80°C. A freshly prepared dose of 1 mg/kg is administered to a second group of mice by daily i.p injections in a volume of 500 μL daily (for 4 days) along with colitis induction (prophylactic approach). A third group of mice receive DSS containing water and daily i.p injections of 0.9% saline (vehicle). The fourth group receive DSS containing water along with daily i.p injections with Dexamethasone (DEX) at doses of 0.01-1.0 mg/kg or its vehicle (0.9% saline) (prophylactic approach). Rats[4] Twenty six ovariectomized female Wistar rats weighing 200±20 g are used. Angiotensin (1-7) is administered intravenously by a microsyringe pump at two different continuous doses of 100 and 300 ng/kg/min after antagonist/saline infusion. Each dose is infused for 15 min; and MAP, RPP, and RBF are recorded during Angiotensin (1-7) infusion and the last 3-5 min of each dose measured as “response to Angiotensin (1-7) infusion”. During Angiotensin (1-7) infusion, RPP is sustained at pre-Ang1-7 infusion levels via an adjustable aortic clamp. At the end of the experiment, the rats are humanely killed by anesthetic overdose, and the left kidneys are removed and weighed immediately. |
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References: [1]. Vaz-Silva J, et al. The vasoactive peptide angiotensin-(1-7), its receptor Mas and the angiotensin-converting enzyme type 2 are expressed in the human endometrium. Reprod Sci. 2009 Mar;16(3):247-56. |
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Ang-(1-7) (H - Asp - Arg - Val - Tyr - Ile - His - Pro - OH) is an endogenous peptide fragment that can be produced from Ang I or Ang II via endo- or carboxy-peptidases respectively[1].
As described for Ang II, Ang-(1-7) also has a broad range of effects in different organs and tissues and goes beyond its initially described cardiovascular and renal actions. Those effects are mediated by Mas and can counter-regulate most of the deleterious effects of Ang II. The interaction Ang-(1-7)/Mas regulates different signaling pathways, such as PI3K (phosphoinositide 3-kinase)/AKT and ERK (extracellular signal-regulated kinase) pathways and involves downstream effectors such as NO, FOXO1 (forkhead box O1) and COX-2 (cyclo-oxygenase-2). Through these mechanisms, Ang-(1-7) is able to improve pathological conditions including fibrosis and inflammation in organs such as lungs, liver and kidney. [2]
In addition, this heptapeptide has positive effects on metabolism, increasing the glucose uptake and lipolysis while decreasing insulin resistance and dyslipidemia. Ang-(1-7) is also able to improve cerebroprotection against ischemic stroke, besides its effects on learning and memory. The reproductive system can also be affected by Ang-(1-7) treatment, with enhanced ovulation, spermatogenesis and sexual steroids synthesis. Finally, Ang-(1-7) is considered a potential anti-cancer treatment since it is able to inhibit cell proliferation and angiogenesis.[2]
References:
1. Santos et al (2000) Angiotensin-(1-7): an update. Regul.Pept. 91 45.
2. Danielle G. P., Thiago V., Robson A. S. Angiotensin-(1-7): beyond the cardio-renal actions. Clinical Science (2013) 124, (443–456)
| Cas No. | 51833-78-4 | SDF | |
| 别名 | Asp-Arg-Val-Tyr-Ile-His-Pro | ||
| 化学名 | Angiotensin (1-7) | ||
| Canonical SMILES | CCC(C)C(C(=O)NC(CC1=CN=CN1)C(=O)N2CCCC2C(=O)O)NC(=O)C(CC3=CC=C(C=C3)O)NC(=O)C(C(C)C)NC(=O)C(CCCN=C(N)N)NC(=O)C(CC(=O)O)N | ||
| 分子式 | C41H62N12O11 | 分子量 | 899 |
| 溶解度 | ≥ 89.9mg/mL in DMSO | 储存条件 | Desiccate at -20°C |
| 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.1123 mL | 5.5617 mL | 11.1235 mL |
| 5 mM | 0.2225 mL | 1.1123 mL | 2.2247 mL |
| 10 mM | 0.1112 mL | 0.5562 mL | 1.1123 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。
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Angiotensin-(1-7), Adipokines and Inflammation
Nowadays the adipose tissue is recognized as one of the most critical endocrine organs releasing many adipokines that regulate metabolism, inflammation and body homeostasis. There are several described adipokines, including the renin-Angiotensin system (RAS) components that are especially activated in some diseases with increased production of Angiotensin II and several pro-inflammatory hormones. On the other hand, RAS also expresses Angiotensin-(1-7), which is now recognized as the main peptide on counteracting Ang II effects. New studies have shown that increased activation of ACE2/Ang-(1-7)/MasR arm can revert and prevent local and systemic dysfunctions improving lipid profile and insulin resistance by modulating insulin actions, and reducing inflammation. In this context, the present review shows the interaction and relevance of Ang-(1-7) effects on regulating adipokines, and as one adipokine itself, modulating body homeostasis, with emphasis on its anti-inflammatory properties, especially in the context of metabolic disorders with focus on obesity and type 2 diabetes mellitus pandemic.
ACE2, Angiotensin 1-7 and skeletal muscle: review in the era of COVID-19
Angiotensin converting enzyme-2 (ACE2) is a multifunctional transmembrane protein recently recognised as the entry receptor of the virus causing COVID-19. In the renin-Angiotensin system (RAS), ACE2 cleaves Angiotensin II (Ang II) into Angiotensin 1-7 (Ang 1-7), which is considered to exert cellular responses to counteract the activation of the RAS primarily through a receptor, Mas, in multiple organs including skeletal muscle. Previous studies have provided abundant evidence suggesting that Ang 1-7 modulates multiple signalling pathways leading to protection from pathological muscle remodelling and muscle insulin resistance. In contrast, there is relatively little evidence to support the protective role of ACE2 in skeletal muscle. The potential contribution of endogenous ACE2 to the regulation of Ang 1-7-mediated protection of these muscle pathologies is discussed in this review. Recent studies have suggested that ACE2 protects against ageing-associated muscle wasting (sarcopenia) through its function to modulate molecules outside of the RAS. Thus, the potential association of sarcopenia with ACE2 and the associated molecules outside of RAS is also presented herein. Further, we introduce the transcriptional regulation of muscle ACE2 by drugs or exercise, and briefly discuss the potential role of ACE2 in the development of COVID-19.
FGF21 Prevents Angiotensin II-Induced Hypertension and Vascular Dysfunction by Activation of ACE2/Angiotensin-(1-7) Axis in Mice
Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity. However, the role of FGF21 in hypertension remains elusive. Here we show that FGF21 deficiency significantly exacerbates Angiotensin II-induced hypertension and vascular dysfunction, whereas such negative effects are reversed by replenishment of FGF21. Mechanistically, FGF21 acts on adipocytes and renal cells to promote induction of Angiotensin-converting enzyme 2 (ACE2), which in turn converts Angiotensin II to Angiotensin-(1-7), then inhibits hypertension and reverses vascular damage. In addition, ACE2 deficiency strikingly abrogates these beneficial effects of FGF21 in mice, including alleviation of Angiotensin II-associated hypertension and vascular damage. Otherwise, pharmaceutical inhibition of Angiotensin-(1-7) attenuates the protective effect of FGF21 on Angiotensin II-induced vascular dysfunction, but not on hypertension. Thus, FGF21 protects against Angiotensin II-induced hypertension and vascular impairment by activation of the ACE2/Angiotensin-(1-7) axis via fine-tuning the multi-organ crosstalk between liver, adipose tissue, kidney, and blood vessels.
Angiotensin-(1-7): Translational Avenues in Cardiovascular Control
Despite decades of research and numerous treatment approaches, hypertension and cardiovascular disease remain leading global public health problems. A major contributor to regulation of blood pressure, and the development of hypertension, is the renin-Angiotensin system. Of particular concern, uncontrolled activation of Angiotensin II contributes to hypertension and associated cardiovascular risk, with antihypertensive therapies currently available to block the formation and deleterious actions of this hormone. More recently, Angiotensin-(1-7) has emerged as a biologically active intermediate of the vasodilatory arm of the renin-Angiotensin system. This hormone antagonizes Angiotensin II actions as well as offers antihypertensive, antihypertrophic, antiatherogenic, antiarrhythmogenic, antifibrotic and antithrombotic properties. Angiotensin-(1-7) elicits beneficial cardiovascular actions through mas G protein-coupled receptors, which are found in numerous tissues pivotal to control of blood pressure including the brain, heart, kidneys, and vasculature. Despite accumulating evidence for favorable effects of Angiotensin-(1-7) in animal models, there is a paucity of clinical studies and pharmacokinetic limitations, thus limiting the development of therapeutic agents to better understand cardiovascular actions of this vasodilatory peptide hormone in humans. This review highlights current knowledge on the role of Angiotensin-(1-7) in cardiovascular control, with an emphasis on significant animal, human, and therapeutic research efforts.