Nitric oxide formation during the cytochrome P-450-dependent reductive metabolism of 18-nitro oxyandrostenedione

1 8-Nitro-oxyandrostenedione (1 8-ONOA), a potential mecha-nism-based inhibitor of the last steps of aldosterone biosyn-thesis, is well recognized by different cytochrome P-450s, which are able to metabolize it reductively into nitric oxide (NO) and 1 8-hydroxyandrostenedione. Rat liver microsomal P-450s are able to carry out this reaction with increased efficiency under anaerobic conditions. P-450 3A isozymes induced upon treatment of rats with dexamethasone or troleandomycin were best able to bind and metabolize 1 8-ONOA. This reaction was shown to occur in the presence of dioxygen as well, suggesting that it may be of physiological relevance. The formation of NO was detected as a transient P-450-Fe(ll)NO complex by UV-visible and EPR spectroscopy. In addition, steroidogenic tis-sues containing cytochrome P-450s such as bovine adrena