PURPOSE: Nitric oxide (NO) and phosphodiesterases (PDEs) play key roles in mediating relaxation of corpus cavernosal smooth muscle by increasing intracellular cGMP level. Here, we investigated effects of NO-donor (sodium nitroprusside, SNP) and penile specific type-V PDE inhibitor (zaprinast) in human and rabbit corpus cavernosal cells and tissues in vitro. MATERIALS AND METHODS: The cultured smooth muscle cells and tissues of human and rabbit corpus cavernosum were treated with increasing concentrations of SNP or zaprinast for 5 and 20 minutes, respectively, and intracellular cGMP levels were measured by radioimmunoassay. Organ bath study was performed to measure the relaxation effects of drugs on precontracted corpus cavernosal muscle strips. RESULTS: Although both NO-donor and type-V PDE inhibitor effectively stimulated the accumulation of cGMP in a dose-dependent manner, magnitude of cGMP increase and specificity of drug were found to be species-dependent. In human corpus cavernosal tissues, cGMP was increased upto 10- and 5-folds by SNP and zaprinast, respectively. However, magnitude of increase was much less in cultured smooth muscle cells. In rabbit, SNP effect was most prominent in cultured cells and effects of SNP and zaprinast were modest in tissues. Both agents also resulted in effective relaxation of human and rabbit cavernosal tissue strips. Similar patterns of dose-response curves were shown between results from the organ bath studies and cGMP radioimmunoassay with cavernosal smooth muscle cells. CONCLUSIONS: Present results show that effects of SNP and zaprinast are not coincident in different species, suggesting possible species-specificities of these two agents. Measurement of cGMP changes in cultured cavernosal smooth muscles cells could be reflected to the relaxation effects of drugs on corpus cavernosal muscle strips.