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Losartan

Manufactured by Merck Group
Sourced in United States, United Kingdom, Germany, Switzerland, Australia, China, Sao Tome and Principe

Losartan is a pharmaceutical compound used as an active ingredient in various prescription medications. It functions as an angiotensin II receptor antagonist, which helps to regulate blood pressure by blocking the action of angiotensin II, a hormone that constricts blood vessels. Losartan is commonly used in the treatment of hypertension and other cardiovascular conditions.

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163 protocols using losartan

1

Angiotensin II and Tumor Growth

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SNK-6 cells were pre-treated with PBS (BioChannel Technology Co., Ltd., Nanjing, China), Ang II (100 nM, Sigma, MO, U.S.A.), losartan (2 μM, Sigma) or Ang II+losartan in serum-free medium for 24 h prior to injection [21 (link)]. Therefore, the mice were randomly divided into four groups injected with SNK-6 cells treated with the above reagents. Tumors were implanted through the subcutaneous injection of SNK-6 cell suspension (about 107) in PBS into the right flank of the mice. Then, Ang II or losartan intraperitoneally injected into the mice every day. Tumor size was measured every 5 days with electronic caliper. Tumor volume (V) was calculated by the formula: V = 0.5 × length × width2 [22 (link)]. After 30 d, the mice were cervical dislocation after anesthetized with isoflurane (2.5%). Death was confirmed by the absence of heartbeat, and corneal reflexes and paw withdrawal response to a noxious pinch. Tumor samples were collected and weighed in all groups.
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2

Differentiation of Podocytes under Angiotensin II

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UdRPCs were cultured in proliferation medium (PM) composed of 50% DMEM high glucose and 50% keratinocyte medium supplemented with 5% FCS, 0.5% NEAA, 0.25% Gtx, and 0.5% penicillin and streptomycin at 37 °C (Gibco, Carlsbad, CA, USA) under hypoxic conditions. For differentiation, the cells were seeded at low (50,000 cells) and high density (350,000 cells) in 6- or 12-well plates coated with 0.2% type 1 collagen (Gibco) and grown in PM for 24 h. After this, the medium was changed to advanced RPMI (Gibco) supplemented with 0.5% FCS, 1% penicillin and streptomycin, and 30 µM retinoic acid. Typical podocyte morphology was observed after 7 days. ANG II and losartan (Sigma-Aldrich, St. Louis, MO, USA) were diluted in the culture medium to a final concentration of 100 µM (ANGII) or 0.01 µM (losartan). Cells were incubated for 6 h and 24 h with ANGII and 48h with losartan, and the conditioned medium was kept for secretome analyses.
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3

Prorenin Signaling Pathway in Renal Cells

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NRK-52E cells (ATCC, Manassas, VA) were cultured and prepared as previously described17 (link). Cells were treated with human recombinant prorenin (Cayman Chemical, Ann Arbor, MI) at 0, 10, 20, 40, 80, and 100 pmol/L for 24 h or 100 pmol/L for 0, 6, 12, 24, and 48 h after preincubation with the Ang II type 1 receptor blocker losartan (10 μmol/L) (Sigma, San Francisco, CA,) or the Ang II type 2 receptor blocker PD123319 (10 μmol/L) (Sigma, San Francisco, CA) for 1 h.
The cells were treated with bafilomycin A1 (1 nmol/L, Sigma-Aldrich), losartan (10 μmol/L), and PD123319 (10 μmol/L) for 1 h before prorenin (100 pmol/L) incubation for 48 h to evaluate the effects of the V-ATPase inhibitor bafilomycin A1 on prorenin-induced FN and α-SMA expression in NRK52E cells. Cells were harvested and used in MTT (3-(4, 5-dimethyl (thiazol-2-yl)-2, 5-diphenyltetrazolium bromide) cell viability, immunoblotting, real-time polymerase chain reaction (PCR), and immunofluorescence assays.
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4

Apolipoprotein E Knockout Mice in CKD

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All experiments were done using female apolipoprotein E knockout (apoE−/−) mice on a C57BL/6 background (Jackson Laboratories, Bar Harbor, ME) maintained on normal mouse chow (RP5015; PMI Feeds, St. Louis, MO) containing 18.9% protein, 11.0% fat, 0.8% calcium, 0.5% phosphate, and 3.3 IU/gm vitamin D3. UNx (n = 40) or sham operation (Sham, n = 10) were performed at 8 weeks of age [11 (link),22 ]. UNx mice were further divided into four groups: no treatment, pioglitazone [Takeda Chemical Industries, Osaka, Japan, 0.016% (w/w) in food, n = 10; UNx + Pio], losartan (Sigma–Aldrich, St. Louis, MO, 100 mg/L in drinking water, n = 10; UNx + Los), and pioglitazone together with losartan (n = 10; UNx + Pio/Los) until sacrifice at 20 weeks of age. Care and experimental procedures were in accordance with National Institutes of Health and Vanderbilt University Institutional Animal Care and Usage guidelines.
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5

Losartan Mitigates Ang II-Induced Podocyte Injury

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In order to examine the effect of losartan on Ang II-induced podocyte injury, podocytes grown under growth-restrictive conditions for 14 days were incubated with media containing 10% FBS in the presence of 10 -6 mol/l losartan (Sigma Chemical Co.). losartan was not removed until the end of each experiment. To determine if losartan reduced a range of injuries, the following experiments were undertaken after one hour of losartan incubation. To determine the mechanisms of podocyte injury induced by Ang II, we exposed podocytes to Ang II (Sigma Chemical Co.) at a concentration of 10 -6 mol/l. Following a 48-hour incubation with Ang II in the presence or absence of losartan, we observed and harvested at eight, 24 and 48 hours, respectively. The experiments were all repeated three times.
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6

Glucose, LPS, and AngII Treatments

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The treatments were divided into five groups: the control group (CON), without any treatment; the high glucose group (HG), treated with a high concentration of glucose (33.3 mmol/L, Thermo-Fisher Biochemical Products, Beijing, China); the high glucose + LPS group (LH), treated with a high concentration of glucose (33.3 mmol/L) and LPS (100 ng/mL, Sigma Aldrich, Saint Louis, Missouri, USA); the high glucose + LPS + AngII group (LHA), treated with a high concentration of glucose (33.3 mmol/L), LPS (100 ng/mL) and AngII (1 × 10 -7 mol/L, Sigma Aldrich, Saint Louis, Missouri, USA); and the high glucose + LPS + Losartan group (LHL), pretreated with Losartan (1 × 10 -7 mol/L, Sigma Aldrich, Saint Louis, Missouri, USA) for 6 h prior to treatment with a high concentration of glucose (33.3 mmol/L) and LPS (100 ng/mL).
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7

Oral Gavage of Antihelminthic Drugs

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Losartan and enalapril were purchased from Sigma-Aldrich, St. Louis, MO, USA). Praziquantel (Biltricide, Alexandria Company for Pharmaceuticals and Chemical Industries, Egypt) was used as a reference drug. Both enalapril and Losartan were dissolved in water, while PZQ was dissolved in 2% Cremophor El (Sigma Chemical Co., St. Louis, USA) by vortexing and then given by oral gavage using a mouse feeding needle, in a volume of 200 μl/mouse.
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8

Airway Epithelial Cell Differentiation

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Culturing of HBECs at the air–liquid interface (ALI) was performed as described (see also online supplementary methods) [18 (link)–20 (link)]. In vitro losartan (no. 61188, Millipore Sigma, St. Louis, MO, USA) treatment in the medium at 10 μM was started the day that P1 HBECs went to an ALI and were maintained throughout differentiation, except for cells from smokers (including COPD) that were treated for 24 h with losartan before CS exposure. LY2157299 (no. S2230, Selleckchem, Houston, TX, USA) at 10 µM or EXP3179 (no. 18855, Cayman Chemicals, Ann Arbor, MI, USA) at 5 µM was added to the basolateral medium of ALI cultures 24 h before CS exposure.
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9

Stox1-KO Pregnancy Mouse Model

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At 8 weeks of age, homozygous Stox1-KO or WT crosses were maintained to produce pregnant mice with Stox1-KO or WT litters, respectively. The vaginal plug day was set as E0.5. For mice receiving losartan therapy, 250 μg of losartan (MilliporeSigma) was injected intraperitoneally daily from E14.5 until sacrifice.
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10

AngII-Induced Cardiomyocyte Remodeling

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Adult rat cardiomyocytes were seeded on laminin pretreated coverslips and then incubated with AngII (1 µM) in the presence or absence of Losartan (100 nM) (Sigma). Subsequently, cardiomyocytes were washed with PBS and fixed with 4% paraformaldehyde. Cardiomyocytes were then permeabilized with 0.02% Triton X-100 in blocking buffer (3% BSA, 5% goat serum in PBS) and incubated for 16 hours with primary antibodies (Anti-CaV1.2, Alomone #ACC-003, rabbit polyclonal, Anti- βarrestin1/2, Santa Cruz #SC-53781, mouse monoclonal, Anti-αActinin, Abcam #AB-9465, mouse monoclonal) before addition of fluorescently labeled secondary antibodies and visualization by confocal microscopy. Intracellular signal percentage was calculated by integrating the cardiomyocyte surface fluorescence (defined by hand for each image) and subtracting it from the total integrated fluorescence. This ensuing signal was then normalized to the total integrated fluorescence.
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