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

Capsule:
Diabetes induces oxidative DNA damage in the corpus cavernosum. Angiotensin-(1–7), a counter-regulator of angiotensin II signaling, significantly attenuates DNA damage and structural changes in the corpus cavernosum.

Authors:
Narayana Kilarkaje, Ph.D., Mariam H.M. Yousif, Ph.D., Ahmed Z. El-Hashim, Ph.D., Batoul Makki, M.Sc., Saghir Akhtar, Ph.D., Ibrahim F. Benter, Ph.D.

Volume 100, Issue 1, Pages 226-233, July 2013

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.

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