Nitric oxide photogeneration from trans-Cr(cyclam)(ONO)(2)(+) in a reducing environment. activation of soluble guanylyl cyclase and arterial vasorelaxation.
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.
Ostrowski
Alexis D
AD
Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106-9510, USA.
Deakin
Sherine J
SJ
Azhar
Bilal
B
Miller
Thomas W
TW
Franco
Nestor
N
Cherney
Melisa M
MM
Lee
Andrea J
AJ
Burstyn
Judith N
JN
Fukuto
Jon M
JM
Megson
Ian L
IL
Ford
Peter C
PC
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*
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