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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

Authors :
Ian L. Megson
Andrea J. Lee
Thomas W. Miller
Nestor E. Franco
Bilal Azhar
Melisa M. Cherney
Jon M. Fukuto
Alexis D. Ostrowski
Judith N. Burstyn
Sherine J. Deakin
Peter C. Ford
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.

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