Chronic Treatment with a Type 5 Phosphodiesterase Inhibitor Suppresses Apoptosis of Corporal Smooth Muscle by Potentiating Akt Signalling in a Rat Model of Diabetic Erectile Dysfunction

ObjectivesTo examine whether chronic treatment with a type 5 phosphodiesterase inhibitor (PDE5I) could suppress corporal apoptosis via potentiation of Akt signalling in diabetic erectile dysfunction.MethodsSprague-Dawley rats (12 wk old) were divided into three groups (n = 12 in each): normal control, diabetes (DM), and diabetes treated with PDE5I (DM+PDE5I). The rats in the diabetic groups received a single injection of streptozotocin (50 mg/kg), and from 8 wk after establishment of diabetes, DM and DM+PDE5I were treated with vehicle and PDE5I (SK-3530, 10 mg/kg), respectively, for 4 wk. After 12 wk of streptozotocin injections, six rats in each group underwent cavernosometry with cavernous nerve electrostimulation (2 V, 0.2 ms, 50 s, 2.5–20 Hz). The penile tissues from the remaining six rats were used for immunohistochemical evaluation of apoptosis, immunoblotting for the phosphorylation of Akt and its downstream molecule Bad, and a colorimetric assay of caspase activity.ResultsRats in the DM group showed markedly lower erectile parameters than those in the control group, whereas rats in the DM+PDE5I group showed normalized results. Despite persistent hyperglycaemia, PDE5I treatment significantly reduced the mean apoptotic index (39.6 ± 4.6 vs. 21.3 ± 1.7, p < 0.05). Densitometry revealed significantly higher levels of Akt and Bad phosphorylation, implying inhibition of pro-apoptotic stimuli. PDE5I treatment also significantly inhibited the activities of cavernosal caspase 3 and caspase 9, the main effectors of apoptosis.ConclusionsChronic treatment with PDE5I activated Akt signalling, which suppressed pro-apoptotic stimuli and maintained erectile function in rat model of diabetic erectile dysfunction.