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The Acute Effect of Trimethylamine-N-Oxide on Vascular Function, Oxidative Stress, and Inflammation in Rat Aortic Rings

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Abstract

A growing body of evidence suggests that the gut microbiota affects the cardiovascular system directly and indirectly via biologically active molecules. TMAO, a key metabolite produced by gut bacteria is implicated in atherosclerosis and chronic endothelial dysfunction, but with an unclear effect on vascular tone, oxidative stress, and inflammation. Our study aimed to evaluate the acute effects of TMAO on vascular contractility in relation with oxidative stress markers and inflammation. Aortic rings were harvested from laboratory rats and placed in a tissue bath system containing TMAO in concentrations of 300, 100, 10 µM, and control. Vascular tone under the influence of vasoconstrictor phenylephrine and non-endothelial-dependent vasodilator sodium nitroprusside was assessed using force transducers connected to a computer-based acquisition system. Oxidative stress and inflammation were quantified by vascular assessment of the activity of NF-κB, NRF2, SOD1, and iNOS by western-blotting and MDA by spectrofluorimetry. After the incubation of the aortic rings in TMAO solutions for 1 h, there was no difference in vasoconstrictor and non-endothelial vasodilator response between the studied doses. TMAO acutely induced oxidative stress and inflammation, significantly increasing levels of MDA and the expression of NF-κB, NRF2, SOD1, and iNOS, mostly in a dose-dependent manner. Our study showed the lack of a short-term effect of studied TMAO doses on vascular contractility, but demonstrated an acute prooxidative effect and activation of major inflammatory pathways, which can partially explain the detrimental effects of TMAO in cardiovascular disease.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the University of Medicine and Pharmacy “Iuliu Hatieganu” of Cluj-Napoca, Romania, through a grant—Proiect Cercetare Doctorala 2019 (PCD 2019), contract number 1529/22 from 18.01.2019.

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Authors and Affiliations

  1. Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor Street, No 1, Cluj-Napoca, Romania

    Cristian Marius Florea, Ioana Baldea, Remus Moldovan, Nicoleta Decea & Gabriela Adriana Filip

  2. Fifth Department of Internal Medicine, Cardiology Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Radu Rosu

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  1. Cristian Marius Florea
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by CF, RM, RR, ND, and AGF. The first draft of the manuscript was written by CF and AGF, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ioana Baldea.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical Approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University of Medicine and Pharmacy “Iuliu Hatieganu” of Cluj-Napoca, Romania and the Sanitary Veterinary Department of Cluj-Napoca, Authorization number 184 from 12.08.2019).

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Florea, C.M., Baldea, I., Rosu, R. et al. The Acute Effect of Trimethylamine-N-Oxide on Vascular Function, Oxidative Stress, and Inflammation in Rat Aortic Rings. Cardiovasc Toxicol 23, 198–206 (2023). https://doi.org/10.1007/s12012-023-09794-6

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