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Angiotensin II human (Angiotensin II) TFA is a vasoconstrictor and a major bioactive peptide of the renin/angiotensin system. Angiotensin II human TFA plays a central role in regulating human blood pressure, which is mainly mediated by interactions between Angiotensin II and the G-protein-coupled receptors (GPCRs) Angiotensin II type 1 receptor (AT1R) and Angiotensin II type 2 receptor (AT2R). Angiotensin II human TFA stimulates sympathetic nervous stimulation, increases aldosterone biosynthesis and renal actions. Angiotensin II human TFA induces growth of vascular smooth muscle cells, increases collagen type I and III synthesis in fibroblasts, leading to thickening of the vascular wall and myocardium, and fibrosis. Angiotensin II human TFA also induces apoptosis. Angiotensin II human TFA induces capillary formation from endothelial cells via the LOX-1 dependent redox-sensitive pathway[1][2][3][4]. | [in vivo]
Angiotensin II human TFA can be used to create models of hypertension and cardiac hypertrophy. In 200-250 g Sprague-Dawley rats, intraperitoneal injection of 5 mL 1 nM Angiotensin II human TFA significantly induces neutrophil recruitment, which peaks at 4 hours and resolves within 24 hours. To specifically investigate the role of AT1 receptors in the pathogenesis of hypertension, osmotic mini-pumps are used to continuously infuse Angiotensin II human TFA (1000 ng/kg/min) into each rat for 4 weeks. This process promotes sodium reabsorption by activating renal AT1 receptors, leading to the development of hypertension[4][5].
1. Induction of hypertension[7] Background
Angiotensin II in humans causes blood vessel constriction, activates the sympathetic nervous system, and promotes inflammatory responses and oxidative stress.
Specific Mmodeling Methods
Mice: C57/BL6J ? male and female ? 12-16 wk old ? 21-27 g
Administration: 800 ng/kg/min, 0.003 mL/min ? 7 days ? sc, osmotic pump implanted subcutaneously
Note
Effect of gender: Chronic ANG II-induced hypertension differs by gender in awake mice. Female mice may be protected from the ANG II-induced increase in blood pressure.
Modeling Indicators Key Factor: Blood pressure ↑ on day 7, blood pressure in male was greater than in female.
Correlated Product(s): / Opposite Product(s): /
2. Induction of Cardiac Hypertrophy[8][9] Background
Angiotensin II activates the AT1 receptor in humans, which activates phospholipase C (PLC) and increases protein synthesis.
Specific Mmodeling Methods
Mice: C57/BL6J ? male ? 8 wk old &bull
Administration: 2 μg/kg/min ? 4 weeks ? sc, osmotic pump implanted subcutaneously
Modeling Indicators Indicator changes: Blood pressure in WT mice increased significantly.
Appearance monitoring: cardiac hypertrophy and fibrosis.
Correlated Product(s): / Opposite Product(s): Eplerenone (HY-B0251) | [IC 50]
AT2 Receptor; AT1 Receptor | [References]
[1] de Gasparo M, et al. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000 Sep;52(3):415-72. PMID:10977869
[2] Fyhrquist F, 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, et al. Angiotensin II induces capillary formation from endothelial cells via the LOX-1 dependent redox-sensitive pathway. Hypertension. 2007;50(5):952-957. DOI:10.1161/HYPERTENSIONAHA.107.096446
[4] Nabah YN, et al. Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines. Circulation. 2004;110(23):3581-3586. DOI:10.1161/01.CIR.0000148824.93600.F3
[5] Crowley SD, 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 |
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