title: Nitric oxide photogeneration from trans-Cr(cyclam)(ONO)(2)(+) in a reducing environment. activation of soluble guanylyl cyclase and arterial vasorelaxation.
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.
authors: Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106-9510, USA.
authors: Alexis D
authors: AD
authors: Ostrowski
authors: Sherine J
authors: SJ
authors: Deakin
authors: Bilal
authors: B
authors: Azhar
authors: Thomas W
authors: TW
authors: Miller
authors: Nestor
authors: N
authors: Franco
authors: Melisa M
authors: MM
authors: Cherney
authors: Andrea J
authors: AJ
authors: Lee
authors: Judith N
authors: JN
authors: Burstyn
authors: Jon M
authors: JM
authors: Fukuto
authors: Ian L
authors: IL
authors: Megson
authors: Peter C
authors: PC
authors: Ford
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D002857:Chromium; D006162:Guanylate Cyclase / Q000378:metabolism*; D006571:Heterocyclic Compounds; D009569:Nitric Oxide / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000528:radiation effects; D010084:Oxidation-Reduction; D055668:Photochemical Processes; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D019163:Reducing Agents; D000071756:Soluble Guanylyl Cyclase; D013438:Sulfhydryl Compounds; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D006571:Heterocyclic Compounds; D020030:Nitric Oxide Donors; D018160:Receptors, Cytoplasmic and Nuclear; D019163:Reducing Agents; D013438:Sulfhydryl Compounds; D002857:Chromium; C024560:cyclam; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase