ArticleRedox biology2016
Omeprazole impairs vascular redox biology and causes xanthine oxidoreductase-mediated endothelial dysfunction.
Article in Redox biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 60 citations in OpenAlex.
- Safety and Efficacy of Benzbromarone and Febuxostat in Hyperuricemia Patients with Chronic Kidney Disease: A Prospective Pilot Study.Clinical and experimental nephrology · 2018Trial
- Proton pump inhibitor use after kidney transplantation and graft outcomes: A matched national cohort study.Medicine · 2026Article
- Esomeprazole Decreases Soluble Fms-like Tyrosine Kinase-1 in Preeclamptic Pregnancy in Rats.International journal of molecular sciences · 2026Article
- Proton Pump Inhibitors and Biomarkers of Haemostasis in Postmenopausal Women: The Buffalo OsteoPerio Study.Basic & clinical pharmacology & toxicology · 2026Article
- Association between exposure to proton pump inhibitors and hypertension: a descriptive and disproportionality analysis of VigiBase.BMJ open · 2025Article
- In Vivo Studies on the Interaction Between Orally Administered Nitrite and Omeprazole: Beyond Proton-Catalyzed S-Nitrosation.Antioxidants (Basel, Switzerland) · 2025Article
- Potential Kidney Risks Associated With Clinical Doses of Omeprazole: In Vivo and In Vitro Studies.Clinical and experimental pharmacology & physiology · 2025Article
- Proton Pump Inhibitor Use and Incident Hypertension in Menopausal Women.Journal of the American Heart Association · 2025Observational
- Disproportionality analysis of drug-induced erectile dysfunction using FAERS database.Scientific reports · 2025Article
- Proton Pump Inhibitor Use and Incident Cardiovascular Disease in Older Postmenopausal Women.Journal of the American Geriatrics Society · 2025Observational
- Omeprazole and Risk of Hypertension: Analysis of Existing Literature and the WHO Global Pharmacovigilance Database.Drugs - real world outcomes · 2024Article
- Inhibitors of gastric acid secretion increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling.Molecular and cellular biochemistry · 2024Article
- Facilitating Nitrite-Derived S-Nitrosothiol Formation in the Upper Gastrointestinal Tract in the Therapy of Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
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- New Insights in the Complexity and Functionality of the Neurovascular Unit.Handbook of experimental pharmacology · 2022Article
- Association of Proton Pump Inhibitors With Higher Risk of Cardiovascular Disease and Heart Failure.Mayo Clinic proceedings · 2021Article
- Abrupt-onset, profound erectile dysfunction in a healthy young man after initiating over-the-counter omeprazole: a case report.Journal of medical case reports · 2021Article
- Omeprazole suppresses endothelial calcium response and eNOS Ser1177 phosphorylation in porcine aortic endothelial cells.Molecular biology reports · 2021Article
- Xanthine Oxidoreductase Inhibitors.Handbook of experimental pharmacology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proton pump inhibitors (PPIs) are widely used drugs that may increase the cardiovascular risk by mechanisms not entirely known. While PPIs increase asymmetric dimethylarginine (ADMA) levels and inhibit nitric oxide production, it is unknown whether impaired vascular redox biology resulting of increased xanthine oxidoreductase (XOR) activity mediates PPIs-induced endothelial dysfunction (ED). We examined whether increased XOR activity impairs vascular redox biology and causes ED in rats treated with omeprazole. We also examined whether omeprazole aggravates the ED found in hypertension. Treatment with omeprazole reduced endothelium-dependent aortic responses to acetylcholine without causing hypertension. However, omeprazole did not aggravate two-kidney, one-clip (2K1C) hypertension, nor hypertension-induced ED. Omeprazole and 2K1C increased vascular oxidative stress as assessed with dihydroethidium (DHE), which reacts with superoxide, and by the lucigenin chemiluminescence assay. The selective XOR inhibitor febuxostat blunted both effects induced by omeprazole. Treatment with omeprazole increased plasma ADMA concentrations, XOR activity and systemic markers of oxidative stress. Incubation of aortic rings with ADMA increased XOR activity, DHE fluorescence and lucigenin chemiluminescence signals, and febuxostat blunted these effects. Providing functional evidence that omeprazole causes ED by XOR-mediated mechanisms, we found that febuxostat blunted the ED caused by omeprazole treatment. This study shows that treatment with omeprazole impairs the vascular redox biology by XOR-mediated mechanisms leading to ED. While omeprazole did not further impair hypertension-induced ED, further studies in less severe animal models are warranted. Our findings may have major relevance, particularly to patients with cardiovascular diseases taking PPIs.
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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.