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Updated: May 13, 2026

Analytical Techniques for Assaying Nitric Oxide Bioactivity
Published on: June 18, 2012
Nitrate tolerance, oxidative stress, and mitochondrial function: another worrisome chapter on the effects of organic
1Division of Cardiology, Mount Sinai and University Health Network Hospitals, and Department of Medicine, University of Toronto, Toronto, Ontario, Canada. jdp@ca.inter.net
Abstract:
A shortcoming in the clinical use of organic nitrates is the development of tolerance. Recent data have suggested that the denitrification of organic nitrates is mediated by mitochondrial aldehyde dehydrogenase and that dysfunction of this enzyme is an important cause of tolerance. In this issue of the JCI, evidence in support of this hypothesis is presented in an in vivo model of nitrate tolerance (see the related article beginning on page 482).
Insights
Organic nitrates are limited by tolerance development. Mitochondrial aldehyde dehydrogenase dysfunction is a key cause of this tolerance, as shown in a new in vivo model.
Area of Science:
- Biochemistry
- Pharmacology
- Cardiovascular Medicine
Background:
- Organic nitrates are crucial in treating cardiovascular conditions.
- Tolerance to organic nitrates limits their long-term clinical efficacy.
- The exact mechanisms underlying nitrate tolerance remain incompletely understood.
Discussion:
- Recent research implicates mitochondrial aldehyde dehydrogenase (ALDH) in organic nitrate metabolism.
- Dysfunction of ALDH may lead to the accumulation of toxic metabolites or reduced efficacy of nitrates.
- This study investigates the role of ALDH in an in vivo model of nitrate tolerance.
Key Insights:
- Evidence presented supports the hypothesis that ALDH dysfunction is a primary driver of organic nitrate tolerance.
- The findings highlight a specific enzymatic pathway crucial for nitrate efficacy.
- This research provides a molecular basis for understanding and potentially overcoming nitrate tolerance.
Outlook:
- Targeting ALDH could offer novel therapeutic strategies to prevent or reverse nitrate tolerance.
- Further research may explore ALDH activity as a biomarker for predicting treatment response.
- Understanding this mechanism could lead to improved treatment protocols for patients requiring organic nitrates.
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