The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats

The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor, DA-8159, on erectile function throughout the quantitative analysis of vascular endothelial cell, smooth muscle (SM), TGF-beta1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 ( 0, 5, 10, 20mg/ kg) was administered orally once a day to diabetic rats. After 8 weeks, immunohistochemistry and computerized image analysis were performed to quantify the percent area within the Corpora Cavernosa occupied by the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure ( MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic rats showed a significant decrease in the SM and endothelial cell content, and an increase in the TGF-beta1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-beta1 expression level were 9.7 +/- 0.7, 4.5 +/- 0.7 and 17.9 +/- 2.1%, respectively. DA-8159 prevented reduction of SM (12.3 +/- 0.4% (5 mg/kg), 13.8 +/- 0.4% ( 20mg/ kg)) and endothelial cell content ( 5.6 +/- 0.5% ( 5 mg/kg), 6.3 +/- 0.6% (20 mg/kg)). Immunoreactivity of TGF-beta1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8 +/- 1.2% ( 5 mg/kg), 9.5 +/- 1.1% ( 20mg/ kg)). Electrostimulation of the cavernous nerve induced significant increase in maximum ICP (62.2 +/- 13.6 mmHg in 10 mg/kg vs 37.5 +/- 17.5 mmHg in diabetic group) and area under the curve of the ratio of ICP/MAP (8891.09 +/- 1957 in 10 mg/kg vs 6315.87 +/- 2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED.