ArticleScientific reports2017
Human dimethylarginine dimethylaminohydrolase 1 inhibition by proton pump inhibitors and the cardiovascular risk marker asymmetric dimethylarginine: in vitro and in vivo significance.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Esomeprazole covalently interacts with the cardiovascular enzyme dimethylarginine dimethylaminohydrolase: Insights into the cardiovascular risk of proton pump inhibitors.Biochimica et biophysica acta. General subjects · 2022Pooled it
- Causal Effects of Plasma Metabolites on Intervertebral Disc Degeneration and Low Back Pain: A Mendelian Randomization Study.Metabolites · 2026Article
- Esomeprazole Decreases Soluble Fms-like Tyrosine Kinase-1 in Preeclamptic Pregnancy in Rats.International journal of molecular sciences · 2026Article
- Interplay between dietary nitrate metabolism and proton pump inhibitors: impact on nitric oxide pathways and health outcomes.Frontiers in nutrition · 2025Review
- Facilitating Nitrite-Derived S-Nitrosothiol Formation in the Upper Gastrointestinal Tract in the Therapy of Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- Development of a HPLC-MS/MS Method to Assess the Pharmacokinetics and Tumour Distribution of the Dimethylarginine Dimethylaminohydrolase 1 Inhibitors ZST316 and L-257 in a Xenograft Model of Triple-Negative Breast Cancer in Mice.Molecules (Basel, Switzerland) · 2023Article
- Are Proton Pump Inhibitors Contributing in Emerging New Hypertensive Population?Pharmaceuticals (Basel, Switzerland) · 2023Review
- Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view.World journal of cardiology · 2023Review
- Does hyperglycemia affect arginine metabolites in critically ill patients? A prospective cohort and in vitro study.Diabetology & metabolic syndrome · 2023Article
- The Association between Proton Pump Inhibitors and Myocardial Infarction: What Do Food and Drug Administration Data Tell Us?Journal of research in pharmacy practiceArticle
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 inhibitor (PPI)-induced inhibition of dimethylarginine dimethylaminohydrolase 1 (DDAH1), with consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA), might explain the increased cardiovascular risk with PPI use. However, uncertainty exists regarding whether clinical PPI concentrations significantly inhibit DDAH1 under linear initial rate conditions, and whether PPI-induced DDAH1 inhibition significantly increases ADMA in humans. DDAH1 inhibition by esomeprazole, omeprazole, pantoprazole, lansoprazole and rabeprazole was determined by quantifying DDAH1-mediated L-citrulline formation in vitro. Plasma ADMA was measured in PPI users (n = 134) and non-users (n = 489) in the Hunter Community Study (HCS). At clinical PPI concentrations (0.1-10 μmol/L), DDAH1 retained >80% activity vs. baseline. A significant, reversible, time-dependent inhibition was observed with lansoprazole (66% activity at 240 min, P = 0.034) and rabeprazole (25% activity at 240 min, P < 0.001). In regression analysis, PPI use was not associated with ADMA in HCS participants (beta 0.012, 95% CI -0.001 to 0.025, P = 0.077). Furthermore, there were no differences in ADMA between specific PPIs (P = 0.748). At clinical concentrations, PPIs are weak, reversible, DDAH1 inhibitors in vitro. The lack of significant associations between PPIs and ADMA in HCS participants questions the significance of DDAH1 inhibition as a mechanism explaining the increased cardiovascular risk reported with PPI use.
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