INHIBITION OF MITOCHONDRIAL RESPIRATION BY SODIUM NITROPRUSSIDE AND THE MECHANISM OF CYANIDE LIBERATION

The influence of sodium nitroprusside (SNP) on mitochondrialrespiration was examined in rat liver mitochondria. The additionof SNP 1 mmol litre^-1 during state 3 respiration inhibited theoxygen uptake by 63.4%. A mixture of SNP 1 mmol litre^-1 andglutathione (GSH) 1 mmol litre^-1 inhibited the oxygen uptakemore markedly (by 75.9%). The cyanide concentrations were 0.01mmol litre^-1 with SNP alone and 0.15 mmol litre^-1 with the mixtureof SNP and GSH. Cyanide production from SNP in the presencevarious reducing agents was studied in potassium phosphate 0.1mol litre^-1 buffer solution (pH 7.4) incubated at 37°. Cyanidewas liberated markedly from SNP in the presence of GSH or ascorbate.Less cyanide was produced in the presence of NADH of NADPH.The rate production of cyanide was dependent entirely upon theconcentration of each reducing agent added. No cyanide was liberatedwhen sodium dithionite or the oxidezed forms of GSH, NAD orNADP were used. It was concluded that SNP is degradated to cyanideby a hydrogen donor and that the cyanide liberated in this mannerinhibits the cytochrome oxidase activity of mitochondria invivo