It has been reported that the incidence of overactive bladder increases with aging, and the micturition interval is shortened in ovariectomized (OVX) model rats. It has also been reported that administration of estrogen to this OVX model rat improved intercontraction intervals (ICI), but postmenopausal estrogen replacement therapy has the risk of carcinogenesis. In this study, in order to explore an effective treatment for age-related overactive bladder, we investigated the effects of a phosphodiesterase (PDE-5) inhibitor, tadalafil, on voiding function in OVX model rats.

Eight-week-old female Wistar–ST rats were divided into Sham, the ovariectomy (OVX) and OVX with tadalafil (OVX + Tad) (n = 8 each group). For OVX surgery, bilateral ovaries were removed under isoflurane anesthesia. The Sham group underwent Sham surgery with laparotomy only. Tadalafil (10 mg/kg/day) was daily administered 1 day after OVX surgery. The voiding function was evaluated after 4 months. Moreover, a cystometrography (CMG) was performed to assess the voiding interval and intravesical pressure (n = 4 each group). Detrusor muscle contraction (n = 4 each group) was measured via isometric tension using bladder tissue. Contraction was induced using acetylcholine and electrical field stimulation (EFS). Bladder weights were measured prior to isometric tension measurements.

Bladder weight was significantly heavier in the OVX group than in the Sham group (Sham group: 92.2 ± 3.8 mg, OVX group: 124.8 ± 10.1 mg). The bladder weight was significantly lighter in the OVX+Tad group than in the OVX group (OVX+Tad group: 88.9 ± 6.9 mg). Based on the CMG (80 μL/min) results, the OVX group tended to shorten the ICI compared to the Sham group (Sham group: 583.0 ± 32.6 seconds, OVX group: 358.8 ± 75.9 seconds). On the other hand, the OVX+Tad group tended to be longer than the OVX group (OVX+Tad group: 603.5 ± 77.5 seconds). On the other hand, there was no significant difference between the Sham group and the OVX group in maximum intravesical pressure (MP) (Sham group: 31.4 ± 3.1 cmH2O, OVX group: 29.5 ± 1.0 cmH2O). In the OVX+Tad group, MP was tended to increase compared with the other groups (OVX+Tad group: 41.2 ± 2.9 cmH2O). As a result of isometric tension study, there was no significant difference in the contractile response of bladder smooth muscle against acetylcholine between the Sham group and the OVX group (Sham group: 403.8 ± 154.3 N/g, OVX group: 348.0 ± 98.0 N/g), but the OVX+Tad group tended to increase compared to the other groups (OVX+Tad group: 580.2 ± 178.6 N/g). There was also no significant difference in the contractile response of bladder smooth muscle against EFS between the Sham group and the OVX group (Sham group: 301.1 ± 190.9 N/g, OVX group: 183.1 ± 89.9 N/g), and the OVX+Tad group tended to increase compared to the other groups (OVX+Tad group: 595.8 ± 338.2 N/g).

After the OVX surgery, the lCI tended to be shortened, and she exhibited overactive bladder-like symptoms. On the other hand, the tadalafil administered rats improved the ICI to the same extent as the Sham group. On the other hand, Tadalafil administration tended to increase the maximum intravesical pressure during micturition and bladder contractility. Previous reports have reported that a decline in female hormones reduces blood flow in the bladder. On the other hand, there is also a report that administration of tadalafil increased bladder blood flow in animal study. Therefore, the present effect of tadalafil is considered to be related to bladder blood flow. In order to clarify the effect of tadalafil in the future, molecular biological measurements and histological examination are needed.

PDE-5 inhibitors may be useful for the treatment of postmenopausal overactive bladder.