Losartan is an angiotensin II receptor antagonist (IC50=20nM). Losartan works by selectively blocking the AT1 receptor of angiotensin II. Losartan can be used for the treatment of hypertension and diabetic nephropathy[1-4].
In vitro, pretreatment of Vero E6 cells with Losartan (1–100μM) for 1 hour, followed by infection with SARS-CoV-2 (MOI=0.01) and culture for 96 hours, Losartan significantly reduced viral nucleoprotein levels and inhibited viral replication[5]. Pretreatment of MV3 cells with Losartan (0.7μM) for 30 minutes, followed by treatment with ATII (100nM), Losartan significantly inhibited NHE1 activity in the cells[6].
In vivo, Losartan (5-50mg/kg; oral administration) was administered to Swiss mice with 5-FU-induced intestinal mucositis for 4 days. Losartan significantly prevented the 5-FU-induced intestinal mucositis effects[7]. Losartan (10mg/kg) was orally administered daily via drinking water to CD2F1 mice bearing C26 cells for 19 days. Losartan prevented tumor-induced muscle mass loss, reduced tumor weight, attenuated myocardial interleukin-6 expression, improved cardiomyocyte calcium signaling, and increased cardiomyocyte contraction speed, contractile function, and blood pressure in tumor-bearing mice[8].
References:
[1] Sica DA, Gehr TW, Ghosh S. Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44(8):797-814.
[2] Burnier M. Angiotensin II type 1 receptor blockers. Circulation. 2001 Feb 13;103(6):904-12.
[3] Ashry O, Schnecko A, Clauss WG, et al. Evidence for expression and function of angiotensin II receptor type 1 in pulmonary epithelial cells. Respir Physiol Neurobiol. 2014 May 1;195:37-40.
[4] Saleh N, Cosarderelioglu C, Vajapey R, et al. Losartan Mitigates Oxidative Stress in the Brains of Aged and Inflamed IL-10-/- Mice. J Gerontol A Biol Sci Med Sci. 2022 Sep 1;77(9):1784-1788.
[5] Nejat R, Sadr AS, Freitas B, et al. Losartan Inhibits SARS-CoV-2 Replication in Vitro. J Pharm Pharm Sci. 2021;24:390-399.
[6] Olschewski DN, Hofschröer V, Nielsen N, et al. The Angiotensin II Type 1 Receptor Antagonist Losartan Affects NHE1-Dependent Melanoma Cell Behavior. Cell Physiol Biochem. 2018;45(6):2560-2576.
[7] Oliveira MMB, de Araújo AA, Ribeiro SB, et al. Losartan improves intestinal mucositis induced by 5-fluorouracil in mice. Sci Rep. 2021 Dec 1;11(1):23241.
[8] Stevens SC, Velten M, Youtz DJ, et al. Losartan treatment attenuates tumor-induced myocardial dysfunction. J Mol Cell Cardiol. 2015 Aug;85:37-47.
Losartan是一种血管紧张素II受体拮抗剂（IC50=20nM）。Losartan可通过选择性阻断血管紧张素II的AT1受体发挥作用。Losartan可用于高血压和糖尿病肾病的相关治疗[1-4]。
在体外，Losartan（1–100μM）预处理Vero E6细胞1小时，随后以SARS-CoV-2（MOI=0.01）感染后培养96小时。Losartan显著降低病毒核蛋白水平，同时抑制病毒复制[5]。Losartan（0.7μM）预处理MV3细胞30分钟，随后以ATII（100nM）处理。Losartan可显著抑制细胞中NHE1的活性[6]。
在体内，Losartan（5-50mg/kg；口服）用于处理由5-FU诱导肠黏膜炎的Swiss小鼠，持续4天。Losartan显著预防了5-FU诱导的肠黏膜炎效应[7]。Losartan（10mg/kg）每日通过饮用水口服处理携带C26细胞的CD2F1小鼠，持续19天。Losartan预防了肿瘤诱导的肌肉质量损失，减少了肿瘤重量，减轻了心肌白细胞介素-6表达，改善了心肌细胞钙信号传导，提高了心肌细胞收缩速度、收缩功能和肿瘤小鼠的血压[8]。