Role of angiotensin II and angiotensin-(1-7) in diabetes-induced oxidative DNA damage in the corpus cavernosum

Objective: To investigate diabetes mellitus (DM)-induced oxidative DNA damage, putative involvement of angiotensin (Ang) II, and possible modulatory effects of Ang-(1-7) in rat corpus cavernosum (CC). Design: In vivo study. Setting: Research laboratory. Animal(s): Adult male Wistar rats. Intervention(s): Streptozotocin-induced diabetic rats received either captopril, losartan (both 300 mg/L in drinking water), or Ang-(1-7) (576 mg/kg/d IP) for a 3-week period immediately before sacrifice at 6 weeks of DM. Main Outcome Measure(s): Histopathological changes in CC were examined in Masson's trichrome-stained tissue sections. Oxidative stress was evaluated by measuring total oxidant status and antioxidant status. The DNA damage was estimated by measuring 8-hydroxy-2'-deoxyguanosine by immunohistochemistry and ELISA. Result(s): The CC smooth muscle degeneration was observed in association with an increase in total oxidant status and a decrease in total antioxidant status in rats with DM. Oxidative DNA damage was significantly increased in both cytoplasm and nuclei of CC in DM. Treatment with captopril, losartan, or Ang-(1-7) inhibited these changes in rats with DM. Conclusion(s): The data indicate that Ang II signaling is involved in DM-induced structural changes and oxidative DNA damage in the CC and that modulation of the signaling by captopril, losartan, and Ang-(1-7) restores the effects of DM. Thus, Ang-(1-7)/MAS1 axis may be a novel therapeutic target for erectile dysfunction in DM. (C)2013 by American Society for Reproductive Medicine.