Hydrogen sulfide inhibits activity of three isoforms of recombinant nitric oxide synthase.

To clarify the presence of cross-talk between H(2)S and NO, we investigated effect of NaHS, an H(2)S donor, on activity of recombinant NO synthase (NOS) isoforms. Activity of all nNOS, iNOS and eNOS was inhibited by NaHS (IC(50): 0.13-0.21 mM). In contrast, Na(2)SO(3), L-cysteine and threo-1,4-dimercapto-2,3-butanediol, a reductant, exerted poor inhibition of NOS activity. Increasing concentrations of tetrahydrobiopterin (BH(4)) reversed the NaHS inhibition of nNOS and eNOS, but not iNOS. Our data thus demonstrate inhibition of three NOS isoforms by NaHS/H(2)S, and suggest involvement of interaction of NaHS/H(2)S with BH(4) in inhibition of nNOS and eNOS, but not iNOS.