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

Fertil Steril. 2013 Jul;100(1):226-33. doi: 10.1016/j.fertnstert.2013.02.046. Epub 2013 Mar 27.

Abstract

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 μg/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / physiology*
  • Angiotensin I / therapeutic use
  • Angiotensin II / physiology*
  • Animals
  • DNA Damage / physiology*
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Male
  • Oxidative Stress / physiology*
  • Penis / pathology
  • Penis / physiology*
  • Peptide Fragments / physiology*
  • Peptide Fragments / therapeutic use
  • Proto-Oncogene Mas
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Signal Transduction / physiology

Substances

  • Mas1 protein, rat
  • Peptide Fragments
  • Proto-Oncogene Mas
  • Angiotensin II
  • Angiotensin I
  • angiotensin I (1-7)