Association of proton pump inhibitor use with endothelial function and metabolites of the nitric oxide pathway: A cross-sectional study.
citrulline
endothelium
flow-mediated dilation
nitric oxide
proton pump inhibitor
Journal
Pharmacotherapy
ISSN: 1875-9114
Titre abrégé: Pharmacotherapy
Pays: United States
ID NLM: 8111305
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
15
10
2020
revised:
14
12
2020
accepted:
21
12
2020
pubmed:
20
1
2021
medline:
7
1
2022
entrez:
19
1
2021
Statut:
ppublish
Résumé
Long-term intake of proton pump inhibitors (PPIs) might increase the risk of cardiovascular events. One suggested mechanism is that PPIs inhibit the enzyme dimethylarginine dimethylaminohydrolase (DDAH) and thereby block the degradation of endothelial asymmetrical dimethylarginine (ADMA). Excess ADMA in turn leads to impaired endothelial nitric oxide (NO) generation. So far, this mechanism has only been established in human cell cultures. Previous studies that examined this pathway in human populations measured circulating ADMA and found no association with PPI use and excess plasma ADMA. But in a recent study, plasma ADMA was not correlated with intracellular ADMA. We therefore focused on changes in plasma citrulline as an indicator for potential DDAH inhibition. We analyzed the association between regular daily PPI intake and flow-mediated dilation (FMD) of the brachial artery as well as plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine using inverse probability weighting to adjust for confounding and censoring. Data of 1298 participants from two independent cohorts of the population-based Study of Health in Pomerania were used. Participants of the population-based Study of Health in Pomerania are a stratified random sample of the study region. Regular daily intake of PPIs. FMD of the brachial artery and plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine. Eighty-seven participants (57.5% female) were regular daily users of PPIs. In the fully adjusted models, associations were identified for FMD and plasma citrulline concentrations. PPI users revealed a 0.99% (95% CI: -1.96 to -0.02) lower FMD and 3.03 µmol/L (95% CI: -4.96 to -1.10) lower plasma citrulline levels as compared to non-users. Our data provide evidence that long-term intake of PPIs might inhibit human DDAH activity, resulting in impaired endothelial NO production and reduced vascular function. In the long run, this might explain an increased risk for cardiovascular diseases associated with long-term PPI use.
Substances chimiques
Proton Pump Inhibitors
0
Citrulline
29VT07BGDA
Nitric Oxide
31C4KY9ESH
Arginine
94ZLA3W45F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
198-204Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.
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