Effect of cyanide on the reaction of nitroprusside with hemoglobin: relevance to cyanide interference with the biological activity of nitroprusside.
The reaction of sodium nitroprusside (SNP) with deoxyhemoglobin (Hb) results in two distinct EPR-detectable species, the one-electron-reduced nitroprusside ion [(CN)5FeNO]3- and nitrosylhemoglobin (HbNO). In the presence of excess cyanide (CN-) only the signal for [(CN)5FeNO]3- is observed. Thus, while free CN- does not interfere with Hb reduction of SNP, it prevents transfer of the NO moiety to Hb. Electrolytic reduction of SNP under similar conditions, however, leads to [(CN)5FeNO]3- and a small amount of [(CN)4FeNO]2- resulting from loss of the CN- trans to the NO. Excess free CN- shifts the equilibrium between these two species toward [(CN)5FeNO]3-, thereby reducing the concentration of [(CN)4FeNO]2-. Thus, [(CN)4FeNO]2- appears to be responsible for the transfer of NO to Hb. Consistent with this mechanism, both [(CN)5FeNO]3- and [(CN)4FeNO]2- are observed when SNP is added to erythrocyte lysates. Under these conditions HbNO is formed more rapidly due to the higher concentration of the latter species with the labile NO. This observation suggests that red blood cell constituents capable of binding CN- shift the equilibrium between the reduced SNP ions toward [(CN)4FeNO]2-. In the reaction of reduced glutathione (GSH) with SNP, [(CN)5FeNO]3- is formed as well as low concentrations of an EPR-detectable GSH-SNP adduct. Excess free CN- introduces a lag in the appearance of these signals, suggesting that GSH mediates SNP reduction by a different mechanism from that of Hb, although it too is inhibited by CN-.(ABSTRACT TRUNCATED AT 250 WORDS)
Wilcox
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Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755.
Kruszyna
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Kruszyna
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Smith
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D000959:Antihypertensive Agents / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology*; D004347:Drug Interactions; D004578:Electron Spin Resonance Spectroscopy; D004912:Erythrocytes / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006454:Hemoglobins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009599:Nitroprusside / Q000378:metabolism / Q000494:pharmacology*
D000959:Antihypertensive Agents; D003486:Cyanides; D006454:Hemoglobins; D009599:Nitroprusside; C002385:linsidomine; D008981:Molsidomine; D005978:Glutathione