Enalapril (MK-421) is an orally active angiotensin-converting enzyme (ACE) inhibitor that is rapidly hydrolyzed in vivo to its active metabolite, Enalaprilat. Enalaprilat effectively dilates blood vessels, lowers blood pressure, and reduces cardiac load by inhibiting the production of angiotensin II[1-2]. Enalapril is applicable in studies of conditions such as hypertension and congestive heart failure[3-4].
In vitro, pretreatment of human umbilical vein endothelial cells (HUVECs) with Enalapril (50μM) for 24h, followed by stimulation with serum from Alzheimer’s disease (AD) patients for 24h, Enalapril significantly suppressed the expression of pro‑apoptotic factors and reduced the apoptosis rate[5]. Pretreatment of human colorectal cancer cells (HCT116, SW620) and primary human colorectal cancer cells (P1–P4) with Enalapril (100μM) for 24–72h, followed by stimulation with 5‑FU (10μM) for 48–72h, significantly inhibited cell proliferation and NF‑κB/STAT3 signaling pathway activity, while also reducing the expression of angiogenesis‑ and epithelial‑mesenchymal transition (EMT)‑related proteins[6].
In vivo, daily intraperitoneal injection of Enalapril (5mg/kg) for 14 days in a bleomycin‑induced (4U/kg) C57BL/6 mouse model of lung injury significantly suppressed the development of bleomycin‑induced pulmonary hypertension, while also reducing pulmonary collagen deposition and inflammatory responses[7]. Oral administration of Enalapril (30mg/kg/day) via drinking water, starting at 12 months of age and continuing until 15 months of age in C57BL/6 mice, significantly improved age‑related decline in multiple organ functions and cognitive‑behavioral performance[8].
References:
[1] Gomez HJ, Cirillo VJ, Smith SG 3rd. Enalapril: benefit-to-risk ratio in hypertensive patients. J Cardiovasc Pharmacol. 1990;15 Suppl 3:S26-9.
[2] McRaith J, Fitz A. Enalapril: a new angiotensin-converting enzyme inhibitor. Iowa Med. 1986 Oct;76(10):482, 484, 486-8.
[3] Cleary JD, Taylor JW. Enalapril: a new angiotensin converting enzyme inhibitor. Drug Intell Clin Pharm. 1986 Mar;20(3):177-86.
[4] Vlasses PH, Larijani GE, Conner DP, et al. Enalapril, a nonsulfhydryl angiotensin-converting enzyme inhibitor. Clin Pharm. 1985 Jan-Feb;4(1):27-40.
[5] Meamar R, Dehghani L, Ghasemi M, et al. Enalapril protects endothelial cells against induced apoptosis in Alzheimer's disease. J Res Med Sci. 2013 Mar;18(Suppl 1):S1-5.
[6] Yang Y, Ma L, Xu Y, et al. Enalapril overcomes chemoresistance and potentiates antitumor efficacy of 5-FU in colorectal cancer by suppressing proliferation, angiogenesis, and NF-κB/STAT3-regulated proteins. Cell Death Dis. 2020 Jun 24;11(6):477.
[7] Ortiz LA, Champion HC, Lasky JA, et al. Enalapril protects mice from pulmonary hypertension by inhibiting TNF-mediated activation of NF-kappaB and AP-1. Am J Physiol Lung Cell Mol Physiol. 2002 Jun;282(6):L1209-21.
[8] Lyu W, Wang H, Du Z, et al. Enalapril mitigates senescence and aging-related phenotypes in human cells and mice via pSmad1/5/9-driven antioxidative genes. Elife. 2025 Aug 28;14:RP104774.
Enalapril (MK-421)是一种具有口服活性的血管紧张素转换酶（ACE）抑制剂，在体内可迅速水解为活性代谢物Enalaprilat，Enalaprilat通过抑制血管紧张素II的生成，有效舒张血管，降低血压，并减轻心脏负荷[1-2]。Enalapril可用于高血压、充血性心力衰竭等疾病的研究[3-4]。
在体外，Enalapril（50μM）预处理人脐静脉内皮细胞（HUVECs）24小时，随后以阿尔茨海默病（AD）患者血清刺激24小时，Enalapril显著抑制促凋亡因子的表达，同时降低细胞凋亡率[5]。Enalapril（100μM）预处理人结直肠癌细胞（HCT116、SW620）及原代人结直肠癌细胞（P1-P4）24-72小时，随后以5-FU（10μM）刺激48-72小时，Enalapril显著抑制细胞增殖和NF-κB/STAT3信号通路活性，同时降低血管生成和上皮-间质转化（EMT）相关蛋白表达[6]。
在体内，Enalapril（5mg/kg）每日一次腹腔注射，用于处理博来霉素（4U/kg）诱导的C57BL/6小鼠肺损伤模型，持续14天。Enalapril显著抑制了博来霉素诱导的肺动脉高压发展，同时减少肺胶原沉积和炎症反应[7]。Enalapril（30mg/kg/day）通过饮水给药，用于处理12月龄开始直至15月龄的C57BL/6小鼠。Enalapril显著改善了与年龄相关的多器官功能衰退和认知行为表现[8]。