ArticleOxidative medicine and cellular longevity2018
The Endothelin Receptor Antagonist Macitentan Improves Isosorbide-5-Mononitrate (ISMN) and Isosorbide Dinitrate (ISDN) Induced Endothelial Dysfunction, Oxidative Stress, and Vascular Inflammation.
Article in Oxidative medicine and cellular longevity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 19 citations in OpenAlex.
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- Preclinical study for the ameliorating effect of l-ascorbic acid for the oxidative stress of chronic administration of organic nitrates on myocardial tissue in high sucrose/fat rat model.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Recent Advances in the Synthesis and Biomedical Applications of Heterocyclic NO-Donors.Molecules (Basel, Switzerland) · 2021Review
- Redox Switches in Noise-Induced Cardiovascular and Neuronal Dysregulation.Frontiers in molecular biosciences · 2021Review
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveOrganic nitrates such as isosorbide-5-mononitrate (ISMN) and isosorbide dinitrate (ISDN) are used for the treatment of patients with chronic symptomatic stable coronary artery disease and chronic congestive heart failure. Limiting side effects of these nitrovasodilators include nitrate tolerance and/or endothelial dysfunction mediated by oxidative stress. Here, we tested the therapeutic effects of the dual endothelin (ET) receptor antagonist macitentan in ISMN- and ISDN-treated animals. METHODS AND
resultsOrganic nitrates (ISMN, ISDN, and nitroglycerin (GTN)) augmented the oxidative burst and interleukin-6 release in cultured macrophages, whereas macitentan decreased the oxidative burst in isolated human leukocytes. Male C57BL/6j mice were treated with ISMN (75 mg/kg/d) or ISDN (25 mg/kg/d) via s.c. infusion for 7 days and some mice in addition with 30 mg/kg/d of macitentan (gavage, once daily). ISMN and ISDN
conclusionISMN/ISDN treatment caused activation of the NOX-2/ET receptor signaling axis leading to increased vascular oxidative stress and inflammation as well as endothelial dysfunction. Our study demonstrates for the first time that blockade of ET receptor signaling by the dual endothelin receptor blocker macitentan improves adverse side effects of the organic nitrates ISMN and ISDN.
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