NANC NEUROTRANSMISSION IN THE BOVINE RETRACTOR PENIS MUSCLE IS BLOCKED BY SUPEROXIDE ANION FOLLOWING INHIBITION OF SUPEROXIDE-DISMUTASE WITH DIETHYLDITHIOCARBAMATE

This study examined the effects of inhibiting Cu/Zn superoxide dismutase with diethyldithiocarbamate (DETCA) on the ability of superoxide generating agents such as pyrogallol, hypoxanthine/xanthine oxidase and LY 83583, to influence NANC relaxation of strips of bovine retractor penis (BRP) muscle. Although pyrogallol (100 mu M) and hypoxanthine (0.3 mM)/xanthine oxidase (64 mU ml(-1)) had little effect on NANC relaxation in control strips, both induced almost complete inhibition following treatment with DETCA (3 mM) for 1 h. Inhibition was due to the actions of superoxide anion since it was blocked by the addition of exogenous superoxide dismutase (250 U ml(-1)). LY 83583 (0.1-30 mu M) produced a concentration-dependent inhibition of NANC relaxation even in control strips and this too was blocked by exogenous superoxide dismutase, but sensitivity to inhibition was enhanced 10-fold following treatment with DETCA. The data suggest that under normal circumstances the NANC neurotransmitter is protected by high levels of tissue superoxide dismutase, and inhibition of this enzyme increases its susceptibility to destruction by superoxide anions. An important impediment to accepting free nitric oxide as the NANC neurotransmitter in the BRP on the basis that superoxide anion-generating agents inhibit the actions of authentic nitric oxide but not those of NANC nerve stimulation has thus been removed.