L-S-NITROSO-BETA,BETA-DIMETHYLCYSTEINE AND D-S-NITROSO-BETA,BETA-DIMETHYLCYSTEINE DIFFERENTIALLY INCREASE CGMP IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS

We examined the effects of the L- and D-isomers of S-nitroso-beta,beta -dimethylcysteine (L- and D-S-nitrosopenicillamine, 10(-7)-10(-5) M) o n the guanosine 3',5'-cyclic monophosphate (cGMP) content of cultured porcine aortic smooth muscle cells and the decomposition of these ster eoisomers to nitric oxide (NO). L-S-nitrosopenicillamine was a more po tent generator of cGMP than D-S-nitrosopenicillamine although both ste reoisomers 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-nitrosopenicill amine generated significant amounts of cGMP. This study shows that the stereoisomeric configuration of S-nitrosopenicillamine is an importan t factor in its biological potency. The data suggest that the extracel lular or intracellular generation of NO is not the only mechanism by w hich this S-nitrosothiol generates cGMP in vascular smooth muscle.