NONADRENERGIC, NONCHOLINERGIC RELAXATION AND LEVELS OF CYCLIC-NUCLEOTIDES IN RABBIT LOWER URINARY-TRACT

Electrical field stimulation at 12 Hz produced urethral relaxation and increased the tissue cyclic GMP content by 111 +/- 36% (n = 6, P < 0.05). Pretreatment with zaprinast (10 mu M) increased the tissue cyclic GMP content in response to electrical stimulation by 160 +/- 56% (n = 7, P < 0.05). The nitric oxide synthase inhibitor N-G-nitro-L-arginine (0.1 mM) and methylene blue (50 mu M) inhibited electrically-induced cyclic GMP accumulation. Methylene blue only partially inhibited urethral relaxation, whereas N-G-nitro-L-arginine caused complete inhibition. Electrical stimulation of urethral preparations did not affect the tissue levels of cyclic AMP. Administration of sodium nitroprusside increased the cyclic GMP content in the urethra and detrusor. Administration of isoprenaline increased the detrusor cyclic AMP content, but no change in urethral cyclic AMP levels could be detected. Cyclic GMP related drugs (sodium nitroprusside, 8-bromo-cyclic GMP) reduced urethral tone by 67-75% and detrusor tone by 13-39%. These results suggest that nerve-induced relaxation of the rabbit urethra is associated with an increase in cyclic GMP, but not cyclic AMP content. Synthesis of NO is essential for both nerve-mediated relaxation and cyclic GMP accumulation. The urethral smooth muscle tissue is more sensitive to cyclic GMP-activating drugs than the detrusor smooth muscle.