Open AccessRole of oxidative stress‐induced systemic and cavernosal molecular alterations in the progression of diabetic erectile dysfunction在糖尿病性勃起功能障碍的进展过程中氧化应激所诱导的全身以及海绵体分子变化的影响
Author(s) -
Castela Angela,
Gomes Pedro,
Domingues Valentina F.,
Paíga Paula,
Costa Raquel,
Vendeira Pedro,
Costa Carla
Publication year - 2015
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.12181
Subject(s) - oxidative stress , diabetes mellitus , enos , medicine , endocrinology , nitrotyrosine , endothelial dysfunction , nitric oxide , nitric oxide synthase
Background Erectile dysfunction ( ED ) is a prevalent complication of diabetes, and oxidative stress is an important feature of diabetic ED . Oxidative stress‐induced damage plays a pivotal role in the development of tissue alterations. However, the deleterious effects of oxidative stress in the corpus cavernosum with the progression of diabetes remain unclear. The aim of this study was to evaluate systemic and penile oxidative stress status in the early and late stages of diabetes. Methods Male W istar streptozotocin‐diabetic rats (and age‐matched controls) were examined 2 (early) and 8 weeks (late) after the induction of diabetes. Systemic oxidative stress was evaluated by urinary H 2 O 2 and the ratio of circulating reduced/oxidized glutathione ( GSH/GSSG ). Penile oxidative status was assessed by H 2 O 2 production and 3‐nitrotyrosine (3‐ NT ) formation. Cavernosal endothelial nitric oxide synthase ( eNOS ) was analyzed by quantitative immunohistochemistry. Dual immunofluorescence was also performed for 3‐ NT and α ‐smooth muscle actin ( α ‐ SMA ) and eNOS – α ‐ SMA . Results There was a significant increase in urinary H 2 O 2 levels in both diabetic groups. The plasma GSH/GSSG ratio was significantly augmented in late diabetes. In cavernosal tissue, H 2 O 2 production was significantly increased in late diabetes. Reactivity for 3‐ NT was located predominantly in cavernosal smooth muscle ( SM ) and was significantly reduced in late diabetes. Quantitative immunohistochemistry revealed a significant decrease in eNOS levels in cavernosal SM and endothelium in late diabetes. Conclusions The findings indicate that the noxious effects of oxidative stress are more prominent in late diabetes. Increased penile protein oxidative modifications and decreased eNOS expression may be responsible for structural and/or functional deregulation, contributing to the progression of diabetes‐associated ED .