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Nitric Oxide Photogeneration from trans-Cr(cyclam)(ONO)2+ in a Reducing Environment. Activation of Soluble Guanylyl Cyclase and Arterial Vasorelaxation
- Source :
- Journal of Medicinal Chemistry. 53:715-722
- Publication Year :
- 2009
- Publisher :
- American Chemical Society (ACS), 2009.
-
Abstract
- The chromium(III) nitrito complex trans-Cr(cyclam)(ONO)(2)(+) (1) is a very promising photochemical precursor for nitric oxide delivery to physiological targets. Here, we demonstrate that visible wavelength excitation of 1 in solutions containing thiol reductants such as the biological antioxidant glutathione (GSH) leads to permanent reaction even under anaerobic conditions, resulting in high quantum yield NO release. The nitric oxide formed under such conditions is sufficient, even at muM concentrations of 1 and using a low-intensity light source, to activate the enzyme soluble guanylyl cyclase (sGC). We also demonstrate that photolysis of 1 in the nM concentration range with a portable blue LED leads to vasorelaxation of porcine coronary arterial rings, a process also attributed to the NO activation of sGC.
- Subjects :
- Chromium
Antioxidant
Swine
medicine.medical_treatment
Inorganic chemistry
Receptors, Cytoplasmic and Nuclear
chemistry.chemical_element
Nitric Oxide
Photochemistry
Nitric oxide
chemistry.chemical_compound
Soluble Guanylyl Cyclase
Heterocyclic Compounds
Drug Discovery
Cyclam
medicine
Animals
Nitric Oxide Donors
Sulfhydryl Compounds
chemistry.chemical_classification
Chemistry
Photodissociation
Arteries
Glutathione
Photochemical Processes
Vasodilation
Guanylate Cyclase
Reducing Agents
Thiol
Molecular Medicine
Soluble guanylyl cyclase
Oxidation-Reduction
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....f42512404d6eeaf0be677af0246ea82c
- Full Text :
- https://doi.org/10.1021/jm9013357