Role of copper in the relaxant action of S-nitrosothiols in the rat anococcygeus muscle

1. The effects of copper chelators were investigated on the relaxant actions of the S-nitrosothiols S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP), the non-S-nitrosothiol nitric oxide (NO) donor sodium nitroprusside (SNP), free radical NO (NO^.) and the nitrergic neurotransmitter in rat isolated anococcygeus muscle. 2. Cumulative additions of GSNO (0.01-100 μmol/L), SNAP (0.001-10 μmol/L), SNP (0.001-1 μmol/L) and NO^. (0.5-5 μmol/L) and electrical field stimulation (EFS; 1-5 Hz, 10 s) of nitrergic nerves in preparations precontracted with guanethidine (10-30 μmol/L) and clonidine (0.01-0.3 μmol/L) produced concentration-dependent relaxations. 3. The Cu[I] chelator neocuproine (10-30 μmol/L) produced concentration-dependent inhibitions of the relaxations to GSNO and SNAP. At 30 μmol/L, neocuprinone had no effect on relaxations to SNP (0.001-1 μmol/L), NO^. (0.5-5 μmol/L) or EFS (1-5 Hz, 10 s). 4. The Cu[II] chelator cuprizone (30 μmol/L) slightly and significantly enhanced relaxations to GSNO and NO^., but had no effect on relaxations to SNAP, SNP or EFS. 5. In conclusion, the results indicate that Cu[I], but not Cu[II], may be involved in the relaxant actions of GSNO and SNAP in the rat anococcygeus muscle.