Phosphodiesterase-9 (PDE9) specifically hydrolyzes
cyclic GMP, and was detected in human corpus cavernosum. However, no previous studies explored the selective PDE9 inhibition with
BAY 73-6691 in corpus cavernosum relaxations. Therefore, this study aimed to characterize the PDE9
mRNA expression in mice corpus cavernosum, and investigate the effects of
BAY 73-6691 in endothelium-dependent and -independent relaxations, along with the nitrergic corpus cavernosum relaxations. Male mice received daily gavage of
BAY 73-6691 (or
dimethylsulfoxide) at 3 mg kg(-1) per day for 21 days. Relaxant responses to
acetylcholine (ACh),
nitric oxide (NO) (as acidified
sodium nitrite; NaNO2
solution),
sildenafil and electrical-field stimulation (EFS) were obtained in corpus cavernosum in control and BAY 73-6691-treated mice.
BAY 73-6691 was also added in vitro 30 min before construction of concentration-responses and frequency curves. PDE9A and PDE5
mRNA expression was detected in the mice corpus cavernosum in a similar manner. In vitro addition of
BAY 73-6691 neither itself relaxed mice corpus cavernosum nor changed the NaNO2,
sildenafil and EFS-induced relaxations. However, in mice treated chronically with
BAY 73-6691, the potency (pEC50) values for ACh, NaNO2 and
sildenafil were significantly greater compared with control group. The maximal responses (Emax) to NaNO2 and
sildenafil were also significantly greater in BAY 73-6691-treated mice.
BAY 73-6691 treatment also significantly increased the magnitude and duration of the nitrergic corpus cavernosum relaxations (8-32 Hz). In conclusion, murine corpus cavernosum expresses PDE9
mRNA. Prolonged PDE9 inhibition with
BAY 73-6691 amplifies the NO-cGMP-mediated cavernosal responses, and may be of therapeutic value for
erectile dysfunction.