A NEW NITRIC-OXIDE (NO) RELEASER - SPONTANEOUS NO RELEASE FROM FK409

The remarkable vasorelaxant and anti-platelet effects of FK409 have be en reported to be due to nitric oxide (NO) release. The purpose of the present study is to investigate the spontaneous NO-releasing pathway of FK409 in aqueous solutions. H-1-NMR spectra of FK409 suggested that the compound underwent a time-dependent elimination of the hydrogen a tom at a-position of the nitro moiety (at the 5-position) in weakly al kaline solutions. In addition, the degradation of FK409 monitored by H PLC showed a pH-dependency accelerating with an increase of pH. These results revealed that the first step in the degradation of FK409 might be the hydroxyl ion-dependent subtraction of the hydrogen atom at the 5-position. On the other hand, NO release from FK409 also exhibited a pH-dependency, and the velocity of NO liberation was markedly enhance d above pH 6. Furthermore, a linear relationship between the rate of F K409 degradation and that of NO formation was observed, indicating tha t the rate-limiting step for NO formation is the same as that for degr adation. Thus, the rate-limiting process of NO formation from FK409 is due to the deprotonation reaction of the hydrogen atom at the 5-posit ion by hydroxyl ions. The deprotonation process appears to be an essen tial step for both FK409 degradation and NO release. On the basis of t he results, a possible kinetic scheme for NO release from FK409 is pro posed.