In vitro functional responses of isolated normal human prostatic tissue to compounds interacting with the cyclic guanosine monophosphate pathway

Objectives. To examine the effects of some nitric oxide-donating agents, as well as the C-type natriuretic peptide (CNP), on isolated human prostatic tissue. To date, guanylyl cyclases and cyclic guanosine monophosphate (cGMP)-degrading phosphodiesterases represent important target proteins for the development of new drugs for the treatment of lower urinary tract symptoms and benign prostatic hyperplasia. Methods. Using the organ bath technique, the effects of sodium nitroprusside, S-nitrosoglutathione, S-nitrosocysteine, linsidomine, and CNP (1 nM to 1.0/10 mu M) on the tension induced by norepinephrine of prostatic tissue strips were investigated. The tissue was also exposed to three different concentrations of the drugs, and the production of cGMP and cyclic adenosine monophosphate (cAMP) was determined. Results. The tension induced by 40 mu M norepinephrine of the isolated prostatic tissue was dose dependently reversed by the drugs. The rank order of potency was sodium nitroprusside more than S-nitrosoglutathione more than linsidomine more than S-nitrosocysteine, which was equal to CNP (1 mu M). The reversal of tension induced by the greatest drug concentrations ranged from 50% relaxation with sodium nitroprusside to 42% relaxation with CNP. The relaxing effects of the drugs were paralleled by a 2-fold to 40-fold and 2-fold to 45-fold increase in tissue levels of cAMP and cGMP, respectively. Conclusions. Our results provide further evidence that cGMP and cAMP are involved in the control of the normal function of human prostatic smooth muscle. Our findings may provide new strategies for future therapeutics used in the treatment of lower urinary tract symptoms and bladder outlet obstruction secondary to benign prostatic hyperplasia.