INVOLVEMENT OF NITRIC-OXIDE AND CYCLIC-GMP IN RABBIT URETHRAL RELAXATION

Soluble and particulate fractions from rabbit urethra converted [C-14] arginine to [C-14]citrulline, indicating the presence of nitric oxide synthase activity in these fractions. Both soluble and particulate nit ric oxide synthase activities were NADPH dependent, and the soluble ac tivity was Ca2+ dependent. Three nitric oxide synthase (NOS) inhibitor s affected transmural nerve stimulation induced relaxation responses i n the rabbit urethra and the activity of soluble nitric oxide synthase with the same rank order of potency, i.e., N-G-nitro-L-arginine (NNA) > N-G-methyl-L-arginine (NMA) > canavanine (CAN). The rank order of p otency with respect to particulate NOS activity was CAN > NMA = NNA. T he relaxation responses to electrical stimulation were accompanied by increases in cyclic GMP. These results suggest that NOS activity found in the soluble fraction of urethral homogenates produces nitric oxide that in turn increases cyclic GMP levels which mediates the relaxatio n responses induced by transmural nerve stimulation in the rabbit uret hra.