Nitric oxide (NO) has been reacted with a variety of nucleophiles to form adducts of widely differing properties, extending our understanding of the electrophilic behavior of NO. Many of these compounds have shown both vasorelaxant activity in isolated rabbit aorta and in vivo hypotensive action on intravenous injection in rats. The in vitro potency was strongly correlated with the amount of nitric oxide these compounds were independently shown to release on spontaneous decompo- sition in physiological buffers, indicating that compounds in this series are of predictable potency based on physicochemical data. The most active of these agents proved comparable in potency to the clinical vasodilators, sodium nitroprusside and nitroglycerin. Duration of action in the in vivo experiments was most prolonged using a slow-release compound, the spermine/NO complex. The nucleophile/NO adducts have been derivatized by attaching alkyl groups or metal ion centers to either or both of the oxygen atoms; the resulting complexes have interesting properties as potential prodrugs. Other tests have shown the diethyl- amine/NO complex to be an inhibitor of platelet aggregation rivaling aspirin in potency. The results show that the nucleophile/NO complexes should be very useful tools for probing the involvement of nitric oxide in a variety of biomedical applications. Nitric oxide has also been shown to be capable of deaminating nucleic acids and their constituent units at pH 7.4 in the presence of air. NO-releasing compounds, including the nucleophile/NO complexes mentioned above and nitroglycerin, have been shown to induce point mutations in bacteria; nearly all the cases identified so far have been GC to AT transitions. The in vivo significance of these genotoxic deamination reactions is currently being evaluated.
