Superoxide-superoxide oxidoreductase activity of the captopril-copper complex.
BACKGROUND
The purpose of this study was to determine whether the interaction of captopril, an angiotensin-converting enzyme inhibitor, with copper could modify the superoxide dismutase activity of this metal. Results may help to explain the interaction of captopril with reactive oxygen species in the stunned myocardium where substantial mobilization of copper and iron in the coronary flow following ischemia has been reported.


METHODS
An assay that generates superoxide anion radicals without the intervention of metal ions was utilized. In addition, direct EPR analysis was applied to assess the redox state of copper during reactions.


RESULTS
Captopril-copper complex inhibited the superoxide-mediated reduction of nitroblue tetrazolium. In addition, captopril-copper complex was able to suppress formazan production by potassium superoxide. Direct EPR analysis showed that copper was reduced to the cuprous state by captopril and remained in this state in the course of the reaction. Captopril was also stable during the dismutation reaction.


CONCLUSIONS
We conclude that cuprous-captopril complex is a catalytic species with properties different from those of Cu(2+) alone. A model in which sulfur acts as electron acceptor/donor in place of the metal is proposed and a mechanism of action for this complex is discussed.
Jay
David
D
Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano #1, 14080 México City, D.F., México. jay@conacyt.mx
García
Elizabeth J
EJ
Avila
María del Carmen
Mdel C
Muñoz
Eduardo
E
Gleason
Roberto
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D002216:Captopril / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D007202:Indicators and Reagents / Q000378:metabolism; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010084:Oxidation-Reduction; D013057:Spectrum Analysis; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007202:Indicators and Reagents; D013481:Superoxides; D009580:Nitroblue Tetrazolium; D003300:Copper; D002216:Captopril; D013482:Superoxide Dismutase