l- and d- S-nitroso- β, β-dimethylcysteine differentially increase cGMP in cultured vascular smooth muscle cells

We examined the effects of the l- and d-isomers of S-nitroso- β, β-dimethylcysteine ( l- and d- S-nitrosopenicillamine, 10 −7–10 −5 M) on the guanosine 3′,5′-cyclic monophosphate (cGMP) content of cultured porcine aortic smooth muscle cells and the decomposition of these stereoisomers to nitric oxide (NO). l- S-nitrosopenicillamine was a more potent generator of cGMP than d- S-nitrosopenicillamine although both stereoisomers equally decomposed to NO. The 10 −7 M concentration of l- or d- S-nitrosopenicillamine did not generate detectable amounts of NO although 10 −7 M l- S-nitrosopenicillamine but not d- S-nitrosopenicillamine generated significant amounts of cGMP. This study shows that the stereoisomeric configuration of S-nitrosopenicillamine is an important factor in its biological potency. The data suggest that the extracellular or intracellular generation of NO is not the only mechanism by which this S-nitrosothiol generates cGMP in vascular smooth muscle.