ArticlePharmaceutical research2008
Synergistic effect of amlodipine and atorvastatin in reversing LDL-induced endothelial dysfunction.
Article in Pharmaceutical research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 38 citations in OpenAlex.
- Trial
- Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?European heart journal · 2010Trial
- From ASCOT to Asia: A More Active and Successful Approach in Preventing Cardiovascular Disease.Acta Cardiologica Sinica · 2026Review
- Review
- Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States.American journal of biomedical science & research · 2022Article
- Clinical impact of statin therapy on vasospastic angina: data from a Korea nation-wide cohort study.Heart and vessels · 2020Observational
- Effects of Fimasartan/Amlodipine Fixed-Dose Combination on Left Ventricular Systolic Function and Infarct Size in Rat Myocardial Infarction Model.Chonnam medical journal · 2019Article
- Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization.BioMed research international · 2016Article
- Amlodipine increased endothelial nitric oxide and decreased nitroxidative stress disproportionately to blood pressure changes.American journal of hypertension · 2014Article
- Role of lipotoxicity in endothelial dysfunction.Heart failure clinics · 2012Review
- Pleiotropic effects of calcium channel blockers.Current hypertension reports · 2012Review
- Current therapeutic strategies to mitigate the eNOS dysfunction in ischaemic stroke.Cellular and molecular neurobiology · 2012Review
- Combining antihypertensive and antihyperlipidemic agents - optimizing cardiovascular risk factor management.Integrated blood pressure control · 2011Article
- Review
- Angiotensin II decreases nitric oxide synthase 3 expression via nitric oxide and superoxide in the thick ascending limb.Hypertension (Dallas, Tex. : 1979) · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeStatins and certain calcium channel blockers may improve nitric oxide (NO) release and endothelial function through various mechanisms, but their combined effects are not well understood.
methodsThe separate versus combined effects of amlodipine (AML) and atorvastatin (AT) on NO and peroxynitrite (ONOO-) were measured in human umbilical vein endothelial cells (HUVEC) in the presence and absence of low-density lipoprotein (LDL) using electrochemical nanosensors.
resultsThe combination of AML (5 micromol/l) and AT (3-6 micromol/l) directly stimulated NO release that was about twofold greater than the sum of their separate effects (p < 0.05). This synergistic activity is attributed to enhanced endothelial NO synthase (eNOS) function and decreased cytotoxic ONOO-. LDL (100 mg/dl) caused a dysfunction of HUVEC manifested by a 60% reduction in NO and an almost twofold increase in ONOO-. Treatment with AML/AT partially reversed the effects of LDL on endothelial function, including a 90% increase in NO and 50% reduction in ONOO-. Small-angle X-ray diffraction analysis indicates that AML and AT are lipophilic and share an overlapping molecular location in the cell membrane that could facilitate electron transfer for antioxidant mechanisms.
conclusionThese findings indicate a synergistic effect of AML and AT on an increase in NO concentration, reduction of nitroxidative stress. Also, AML/AT partially restored the NO level of LDL-induced dysfunctional endothelium. Their combined effects may be enhanced by antioxidant properties related to their intermolecular actions in the cell membrane and an increase in the expression and coupling of endothelial nitric oxide synthase.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.