Evidence that the nitrergic neurotransmitter and endothelium-derived relaxing factor might be S-nitrosothiols in the mouse corpus cavernosum

The effects of thimerosal, a sulfhydryl oxidizing agent on nitrergic, endot helium-dependent and -independent relaxations were investigated to examine the possibility that the nitrergic neurotransmitter and endothelium-derived relaxing factor (EDRF) could be S-nitrosothiol or free nitric oxide (NO) i n the isolated mouse corpus cavernosum, Thimerosal (5 X 10(-6) - 2 X 10(-5) M) inhibited or almost abolished electrical field stimulation-(EFS, 30V, 0 .5 ms, 15 sec, 1, 2, 4, 8, 16 Hz), acetylcholine-(ACh, 5 X 10(-8) - 1.25 X 10(-6) M), glyceryl trinitrate-(GTN, 3 X 10(-7) - 3 X 10(-6) M), and S-nitr osoglutathione-(GSNO, 5 X 10(-6) - 1.25 X 10(-4) M) induced relaxations, Th iomerosal inhibition seems to be specific to L-arginine NO pathways since i t had no effect on acidified sodium nitrite-(10(-4) - 5 X 10(-4) M), photoa ctivated sodium nitrite-(2 X 10(-4) M), isoprenaline-(10(-6) M), or papaver ine-(10(-4) M) elicited relaxations. Moreover, the inhibitory effect of thi merosal on the nitrergic, ACh- or GTN-induced relaxations were partly rever sed by sulfhydryl-containing compounds, L-cysteine (10(-3) M), dithiothreit ol (10(-3) M), or glutathione (10(-3) M). However L-methionine (10(-3) M), which contains a methyl group on the sulphur atom, failed to restore the th imerosal inhibition. Thimerosal did not change the contraction produced by 10(-4) M N-G-nitro-L-arginine methyl ester, These findings indicate that th e nitrergic neurotransmitter as well as EDRF may not be free NO but NO-tran sferring molecules, probably S-nitrosothiols,in the mouse corpus cavernosum .