title: Role of angiotensin II and angiotensin-(1-7) in diabetes-induced oxidative DNA damage in the corpus cavernosum.
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).
  
  
  METHODS
  In vivo study.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Adult male Wistar rats.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anatomy, Faculty of Medicine, Kuwait University, Safat, Kuwait.
authors.forename: Narayana
authors.initials: N
authors.lastname: Kilarkaje
authors.forename: Mariam H M
authors.initials: MH
authors.lastname: Yousif
authors.forename: Ahmed Z
authors.initials: AZ
authors.lastname: El-Hashim
authors.forename: Batoul
authors.initials: B
authors.lastname: Makki
authors.forename: Saghir
authors.initials: S
authors.lastname: Akhtar
authors.forename: Ibrahim F
authors.initials: IF
authors.lastname: Benter
mesh_terms: D000803:Angiotensin I / Q000502:physiology* / Q000627:therapeutic use; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D004249:DNA Damage / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D010413:Penis / Q000473:pathology / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology* / Q000627:therapeutic use; D000090063:Proto-Oncogene Mas; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology
chemical_list: C000715472:Mas1 protein, rat; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)