Mechanism of action of some inhibitors of endothelium-derived relaxing factor
Open accessAbstract
The mechanism of the inhibitory action of phenidone, 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW 755C), dithiothreitol, hydroquinone, and pyrogallol on the vascular relaxation induced by endothelium-derived relaxing factor (EDRF) was investigated. EDRF was released from porcine aortic endothelial cells in culture and bioassayed on a cascade of superfused rabbit aortic strips. These compounds inhibited EDRF-induced relaxation of vascular strips, without affecting the relaxation induced by glyceryl trinitrate, and their inhibitory potency was markedly attenuated (by more than 1 order of magnitude) by the addition of superoxide dismutase (5-15 units/ml) or oxidized cytochrome c (20-40 microM) but not by catalase (30 units/ml) or heat-inactivated superoxide dismutase. These data indicate that the above five inhibitors inactivate EDRF through the formation of superoxide ions, which have recently been shown to destroy EDRF. The inhibition of EDRF by these compounds is therefore attributable to their redox properties rather than to any specific biological action.
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- Authors
- Moncada, S., Palmer, R. M., & Gryglewski, R. J.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1986-12
- Volume
- 83
- Issue
- 23
- Pages
- 9164-9168
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC387095
- OpenAlex
- W2076583182
- Cited by
- 219
- References
- 20
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 3 · 2020: 2 · 2019: 4 · 2018: 3 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 6
- FWCI
- 14.09
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- endothelium-derived relaxing factor, nitric oxide, nitric oxide inhibitors, phenidone, BW755C, dithiothreitol, hydroquinone, pyrogallol, superoxide, superoxide dismutase, oxidized cytochrome c, vasorelaxation, porcine aortic endothelial cells, nitroglycerin
- MeSH terms
- Animals, Cytochrome c Group, Dithiothreitol, Endothelium, Hydroquinones, Muscle, Smooth, Vascular, Nitric Oxide, Oxidation-Reduction, Pyrazoles, Pyrogallol, Superoxide Dismutase, Swine, Vasodilator Agents, 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine, In Vitro Techniques
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