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.