Mitochondrial oxidative stress and nitrate tolerance
Author Information
Author(s): Mollnau Hanke, Wenzel Philip, Oelze Matthias, Treiber Nicolai, Pautz Andrea, Schulz Eberhard, Schuhmacher Swenja, Reifenberg Kurt, Stalleicken Dirk, Scharffetter-Kochanek Karin, Kleinert Hartmut, Münzel Thomas, Daiber Andreas
Primary Institution: Johannes Gutenberg-University, Mainz, Germany
Hypothesis
The study aims to characterize the role of mitochondria as a source of superoxide formation for the development of in vivo nitrate tolerance in response to GTN.
Conclusion
Chronic GTN infusion stimulates mitochondrial ROS production, which is an important mechanism leading to tolerance and cross-tolerance, while PETN does not induce such oxidative stress.
Supporting Evidence
- Chronic GTN infusion led to impaired vascular responses and increased ROS formation in mitochondria.
- PETN infusion did not increase mitochondrial ROS formation or decrease ALDH-2 activity.
- PETN increased heme oxygenase-1 mRNA in endothelial cells.
Takeaway
When mice were given nitroglycerin, it made their blood vessels less responsive over time because of stress in their cells. But another drug, PETN, didn't cause this problem.
Methodology
The study involved inducing tolerance in mice through chronic infusion of GTN and PETN, followed by measuring vascular reactivity and mitochondrial ROS formation.
Potential Biases
Potential bias due to the involvement of authors affiliated with pharmaceutical companies.
Limitations
The study was conducted on a specific mouse model, which may limit the generalizability of the findings to humans.
Participant Demographics
Male mice aged 7–10 months on a mixed genetic background (C57Bl/6 × 129/Ola).
Statistical Information
P-Value
p<0.001
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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