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-ß1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 (0, 5, 10, 20?mg/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-ß1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-ß1 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%(20?mg/kg)) and endothelial cell content (5.6±0.5%(5?mg/kg), 6.3±0.6%(20?mg/kg)). Immunoreactivity of TGF-ß1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8±1.2%(5?mg/kg), 9.5±1.1%(20?mg/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.International Journal of Impotence Research (2005) 17, 134-141. doi:10.1038/sj.ijir.3901295 Published online 2 December 2004 [ABSTRACT FROM AUTHOR]