THE FORMATION OF NITRIC-OXIDE DONORS FROM PEROXYNITRITE

1 Administration of peroxynitrite (ONOO-, 30-300 mu M) caused relaxati on of rabbit aortic strips superfused in series in a cascade. The comp ound responsible for this effect had a half-life greater than 20 s and could not therefore be either nitric oxide (NO) or ONOO- which have h alf-lives in the order of 1-2 s under these conditions. However the re laxation was inhibited by oxyhaemoglobin, suggesting that the compound could be converted to NO in the vascular tissues or in the superfusat e. 2 The products of the reaction between ONOO- and Krebs buffer conta ining 11 mM glucose, but not glucose-free Krebs buffer, caused relaxat ion of the bioassay tissues. These data suggest that stable NO donor(s ) were formed from the reaction of ONOO- with glucose. We therefore pr epared these NO donor(s) by the reaction of glucose solutions with ONO O- in order to characterize their pharmacological actions both in the cascade bioassay and on platelets and to study their ability to releas e NO. 3 These reaction product(s) caused relaxation in the cascade and inhibition of platelet aggregation. Both effects were dependent on th e concentration of D-glucose, were equally effective if L-glucose was used as a reactant and were reversed by oxyhaemoglobin. 4 The products of the reaction between ONOO- and glucose or other biological molecul es containing an alcohol functional group, such as fructose, glycerol, or glyceraldehyde, released NO in the presence of Cu2+ and L-cysteine . 5 These results indicate that ONOO- reacts with sugars or other comp ounds containing an alcohol functional group(s) to form NO donor(s) wi th the characteristics of organic nitrate/nitrites. This may represent a further detoxification pathway for ONOO- in vivo.