Acceleration of nitric oxide (NO) release from FK409, a spontaneous NO releaser, in the presence of sulfhydryl-bearing compounds

Purpose: Recently, we have reported that FK409 spontaneously releases nitric oxide (NO) in solution. In the present study, the influence of L-cysteine (Cys) and glutathione (CSH), which are typical sulfhydryl group-bearing compounds, on NO release from FK409 and biological action of FK409 was examined. Methods. We evaluated the effects of Cys and GSH on NO release from FK409 by nitrite analysis or detection with a chemiiluminesence analyzer. In a biological study, the influence of Cys on inhibition of rat platelet aggregation of FK409 was investigated. In addition, the above mentioned characteristics of FK409 were compared with those of isosorbide dinitrate (ISDN). Results. FK409 decomposed spontaneously with generation of nitrite in solution. Both Cys and GSH accelerated decomposition of FK409 and nitrite generation from FK409 in a concentration-dependent manner. When the NO levels in the headspace of FK409 solutions (0.5 mM) reached equilibrium with and without 25 mM Cys, the constant rate for NO release from FK409 in the presence of Cys was 13 times larger than that in the absence of Cys. In biological study, FK409 (100 mu M) showed 56 and 90% inhibition of rat platelet aggregation in the absence and presence of 10 mM Cys, respectively, whereas ISDN (100 mu M) showed 10 and 23% inhibition, respectively. Conclusions. Decomposition of FK409 with generation of NO is spontaneous, and is accelerated in the presence of sulfhydryl group-bearing compounds, thereby potentiating the biological action of FK409.