Candesartan

Manufactured by Bio-Techne

Sourced in United Kingdom

Candesartan is a laboratory product provided by Bio-Techne. It is a chemical compound used for research and analytical purposes. The core function of Candesartan is to serve as a reference standard or analytical tool for research applications.

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Close spelling variants of this product

Candesartan cilexetil

7 protocols using candesartan

Candesartan Treatment for Traumatic Brain Injury

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In both studies (C, D) candesartan, a specific AT1 inhibitor was applied. candesartan (CV-11974; Tocris bioscience; Bristol, UK) and the vehicle solution were prepared and applied as previously described^{8 (link)}: The crystalline form of the active drug candesartan was dissolved prior each set of experiments in 0.037 M Na₂CO₃ (vehicle solution) in a concentration of 10 µg/mL. The animals received 0.1 mg/kg candesartan (Cand) or vehicle solution (Veh) by subcutaneous (s.c.) injection 30 min after experimental TBI, followed by a daily injection, 24 and 48 h after TBI.

Timaru-Kast R., Coronel-Castello S.P., Krämer T.J., Hugonnet A.V., Schäfer M.K., Sebastiani A, & Thal S.C. (2023). AT 1 inhibition mediated neuroprotection after experimental traumatic brain injury is dependent on neutrophils in male mice. Scientific Reports, 13, 7413.

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Selective AT2R Agonist C21 in Research

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The specific and selective AT2R agonist, C21 (K_i: 0.4 nM), was provided by Vicore Pharma AB (Göteborg, Sweden). Nitric oxide synthase inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME), was purchased from Sigma Aldrich Co. (St. Louis, United States). The AT1R antagonist, candesartan, and alpha (α)₂-adrenergic receptor agonist, clonidine, were purchased from Tocris Bioscience (Bristol, United Kingdom). Perfusion doses of C21, L-NAME, candesartan and clonidine were based on previous studies (Ogawa et al., 1995 (link); Yang et al., 2005 (link); Mertens et al., 2011 (link); Brouwers et al., 2015 (link)).

Légat L., Smolders I.J, & Dupont A.G. (2019). Investigation of the Role of AT2 Receptors in the Nucleus Tractus Solitarii of Normotensive Rats in Blood Pressure Control. Frontiers in Neuroscience, 13, 589.

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Investigating Angiotensin II Signaling Pathways

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Ang II, bicuculline and N(ω)-nitro-L-arginine methyl ester (L-NAME) were purchased from Sigma Aldrich, Co. (St. Louis, MO, United States). Ang II was used as an AT1R agonist, bicuculline as a GABA_A receptor antagonist and L-NAME as an inhibitor of NO-synthase (NOS). Candesartan was used as a competitive-insurmountable AT1R antagonist (Tocris Bioscience, Bristol, United Kingdom). Infusion doses of Ang II, bicuculline, L-NAME and Candesartan were selected based on previous studies (Ogawa et al., 1995 (link); Smolders et al., 1995a (link); Mertens et al., 2010 (link); Brouwers et al., 2015 (link)).
The treatment compounds [Ang II (1 and 3 μg μL⁻¹ h⁻¹), Candesartan (0.5 and 1.5 ng μL⁻¹h⁻¹), Ang II (1 and 3 μg μL⁻¹ h⁻¹) + Candesartan (0.5 ng μL⁻¹ h⁻¹), Ang II (3 μg μL⁻¹ h⁻¹) + Candesartan (1.5 ng μL⁻¹ h⁻¹), Ang II (3 μg μL⁻¹h⁻¹) + bicuculline (4 μg μL⁻¹ h⁻¹), bicuculline (4 μg μL⁻¹ h⁻¹), Ang II (3 μg μL⁻¹ h⁻¹) + L-NAME (0.4 μg μL⁻¹ h⁻¹), L-NAME (0.4 μg μL⁻¹ h⁻¹)] were dissolved in modified Ringer’s solution (147 mM NaCl, 2.3 mM CaCl₂, 4 mM KCl) and perfused at a flow rate of 2 μL min⁻¹ through the microdialysis probe.

Légat L., Smolders I, & Dupont A.G. (2019). AT1 Receptor Mediated Hypertensive Response to Ang II in the Nucleus Tractus Solitarii of Normotensive Rats Involves NO Dependent Local GABA Release. Frontiers in Pharmacology, 10, 460.

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Isolation and Culturing of Adult Neural Stem Cells

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NSCs were isolated from the V-SVZ of the lateral ventricle of adult young (3–4 months old), aged (20 months old) male mice, or young AT1-KO and AT2-KO mice as previously described [49 (link),50 (link)]. Primary neurospheres were counted after 7 days in vitro. For passages, neurospheres were mechanically dissociated to a single-cell suspension and reseeded in growth media supplemented with the specific treatments: Ang II (100 nM; Sigma-Aldrich); ZD7155 or candesartan (AT1 receptor blockers; 1 μM; Tocris, Bristol, United Kingdom); PD123319 (AT2 receptor blocker; 1 μM; Sigma-Aldrich); CGP42112A (Sigma-Aldrich) or C21 (AT2 receptor agonists; 1 μM); Ang1-7 (1 μM; Sigma-Aldrich); and A779 (MasR blocker; 1 μM; Bachem, Bubendorf, Switzerland). The doses were selected according to suggestions from previous studies [33 (link),35 (link),51 (link),52 (link),53 (link),54 (link),55 (link)]. The diameters of primary and secondary neurospheres were measured after 7 or 5 days, respectively.

Garcia-Garrote M., Perez-Villalba A., Garrido-Gil P., Belenguer G., Parga J.A., Perez-Sanchez F., Labandeira-Garcia J.L., Fariñas I, & Rodriguez-Pallares J. (2019). Interaction between Angiotensin Type 1, Type 2, and Mas Receptors to Regulate Adult Neurogenesis in the Brain Ventricular–Subventricular Zone. Cells, 8(12), 1551.

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Antibody-based Cardiac Glycoside Assay

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Ouabain and candesartan were purchased from Tocris (St. Louis, MO). Digibind, an FDA approved antibody against cardioglycosides was purchased from GlaxoSmithKline (Parma, Italy). The monoclonal antibody against NKA (α6F) developed by Dr. D.M. Fambrough was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of NIHCD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. Phospho- and total EGFR, Src, and ERK1/2 antibodies were purchased from Cell Signaling. Antibodies against angiotensin converting enzyme (catalog number GTX100923, ACE) were purchased from GeneTex (Irvine, CA) and against angiotensinogen (catalog number ab198180, AGT) were purchased from Abcam (Cambridge, MA). HRP-linked secondary antibodies were purchased from Vector laboratories. Streptavidin agarose resin was purchased from Pierce Biotechnology (Rockford, IL). Phosphatase inhibitor cocktail -1 and protease inhibitor cocktail were purchased from Sigma (St. Louis, MO). All other chemicals were purchased from Sigma, unless otherwise specified.

Ketchem C.J., Conner C.A., Murray R.D., DuPlessis M., Lederer E.D., Wilkey D., Merchant M, & Khundmiri S.J. (2016). Low Dose Ouabain Stimulates Na-K ATPase α1 subunit Association with Angiotensin II Type 1 Receptor in Renal Proximal Tubule Cells. Biochimica et biophysica acta, 1863(11), 2624-2636.

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High-throughput Ligand Binding Assay

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TAMRA‒AngII was purchased from AnaSpec. BODIPY FL‒prazosin, biotinylated EGF conjugated to Alexa Fluor 488 streptavidin, and Alexa Fluor 488–conjugated human transferrin were bought from Thermo Scientific. BODIPY FL‒SKF83566 and BODIPY FL‒(S)-propranolol were from HelloBio. Candesartan and SCH 23390 were purchased from Tocris. [Sar¹,Ile⁴,Ile⁸]-angiotensin II was bought from Bachem. The compound library consisting of randomly selected 180 molecules was from BioAscent. Native coelenterazine and coelenterazine h were from Regis Technologies. Furimazine and the Luciferase Assay System were from Promega; DeepBlueC (coelenterazine 400a) was from Perkin-Elmer. Fura-2/AM was from Molecular Probes. ICI118,552 EGF, transferrin, angiotensin II, A61603, prazosin, and otherwise not stated materials were from Sigma-Aldrich.

Tóth A.D., Garger D., Prokop S., Soltész-Katona E., Várnai P., Balla A., Turu G, & Hunyady L. (2021). A general method for quantifying ligand binding to unmodified receptors using Gaussia luciferase. The Journal of Biological Chemistry, 296, 100366.

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Candesartan Administration in Traumatic Brain Injury

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candesartan can cross the blood brain barrier (Nishimura et al., 2000 (link)) so we administered it peripherally either through intraperitoneal (i.p.) injection (3 day cohort), or osmotic minipump (29 day cohort). candesartan was resuspended in 0.1N Na₂CO_3, pH 7.4, and administered at 0.1 mg/kg/day. All mice received their first dose of either candesartan (Tocris Bioscience, Minneapolis, MN, United States # 4791) or vehicle (0.9% saline and 0.1N Na₂CO₃ at pH = 7.4) six hours after the CCI or sham procedure through i.p. injection. Mice in the 3 day cohort received two subsequent i.p. injections at 24- and 48-h after CCI, before sacrifice at 3 dpi. Mice in the 29-day cohort were surgically implanted with an osmotic pump (#1004, Alzet, Cupertino, CA, United States) 24 h after the CCI or sham procedure. Pumps were placed in the lower back through a tunneled incision at the base of the neck under isoflurane anesthesia. Prior to implantation the osmotic pumps were primed with candesartan or vehicle at 37°C overnight.

Attilio P.J., Snapper D.M., Rusnak M., Isaac A., Soltis A.R., Wilkerson M.D., Dalgard C.L, & Symes A.J. (2021). Transcriptomic Analysis of Mouse Brain After Traumatic Brain Injury Reveals That the Angiotensin Receptor Blocker Candesartan Acts Through Novel Pathways. Frontiers in Neuroscience, 15, 636259.

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