Various intracellular compartments cooperate in the release of nitric oxide from glycerol trinitrate in liver
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1. Glycerol trinitrate (GTN) has been used in therapy for more than 100 years. Biological effects of GTN are due to the release of the biomediator nitric oxide (NO). However, the mechanism by which GTN provides NO, in particular in liver, is still unknown. In this study, we provide experimental evidence showing that cytoplasm, endoplasmic reticulum, and mitochondria are required for the release of NO from GTN in the liver. 2. NO and nitrite (NO(2)(-)) were determined using low-temperature electron paramagnetic resonance and the Griess reaction, respectively. 3. The first step of GTN biotransformation is the release of NO(2)(-). This step is performed in cytoplasm and catalyzed by glutathione-S-transferase. The second step is the rate-limiting step where NO(2)(-) is slowly reduced to NO. This is mainly catalyzed by cytochrome P-450. The second phase can be significantly enhanced by decreasing the pH value, a situation which occurs during ischemia. At high NADPH concentrations exceeding physiological values, cytochrome P-450 catalyzes GTN biotransformation without the involvement of cytoplasmic glutathione-S-transferase. 4. In conclusion, our data show that NO(2)(-) derived from the first step of biotransformation of GTN in the liver is the precursor of NO but not a product of NO degradation; consequently, NO(2)(-) levels are not likely to be a marker of NO release from GTN as earlier suggested.
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Dietary NO3− supplementation elevates nitric oxide bioavailability via reduction of exogenous NO3− to nitrite by commensal anaerobic bacteria in the oral cavity, followed by one-electron reduction of NO2− to NO catalyzed by various NO2− reductases in tissue and blood.
“Dietary NO3− supplementation has been observed to elevate nitric oxide (NO) bioavailability via the reduction of exogenous NO3− to nitrite (NO2−) by commensal anaerobic bacteria in the oral cavity [79], followed by the one-electron reduction of NO2− to NO (and other nitrogen intermediates) catalyzed by various NO2− reductases [80,81,82,83,84] in the tissue and blood.”
From Effects of Dietary Nitrate Supplementation on Weightlifting Exercise Performance in Healthy Adults: A Systematic Review (2020) · cites this paper as [81]
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Nitric Oxide Formation from Inorganic Nitrate and Nitrite
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Impact of mitochondria on nitrite metabolism in HL-1 cardiomyocytes
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Exercise and peripheral vascular function in health and disease
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Nitric oxide functions in the heart
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- Authors
- Kozlov, A. V., Dietrich, B., & Nohl, H.
- Affiliations
- University of Veterinary Medicine Vienna (AT)
- Corresponding author
- Kozlov, Andrey V
- ORCID
- Kozlov, Andrey V
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2003-07
- Volume
- 139
- Issue
- 5
- Pages
- 989-997
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1573917
- OpenAlex
- W2080721489
- Cited by
- 69
- References
- 43
- Citations by year
- 2024: 2 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 6 · 2015: 3 · 2014: 3 · 2013: 7 · 2012: 6
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- glycerol trinitrate, nitric oxide release, liver, nitrite, nitrate, glutathione S-transferase, cytochrome P450, NADPH, intracellular compartments, endoplasmic reticulum, mitochondria, cytoplasm, drug metabolism, ischemia, pH
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Endoplasmic Reticulum, Nitroglycerin, Intracellular Fluid, Liver, Male, Mitochondria, Nitric Oxide, Nitrites, Rats, Sprague-Dawley, Rats
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