Role of oxidative stress-induced systemic and cavernosal molecular alterations in the progression of diabetic erectile dysfunction

• Published in: Journal of diabetes 2015-05, Vol.7 (3), p.393-401
• Main Authors: Castela, Angela, Gomes, Pedro, Domingues, Valentina F, Paíga, Paula, Costa, Raquel, Vendeira, Pedro, Costa, Carla
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - pathology; Disease Progression; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Erectile Dysfunction - etiology; Erectile Dysfunction - pathology; Fluorescent Antibody Technique; Immunoblotting; Male; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Nitric Oxide Synthase Type III - metabolism; Oxidative Stress; Penis - metabolism; Penis - pathology; Rats; Rats, Wistar; Tyrosine - analogs & derivatives; Tyrosine - metabolism
• ISSN: 1753-0407
• DOI: 10.1111/1753-0407.12181

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. Male Wistar 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 H2 O2 and the ratio of circulating reduced/oxidized glutathione (GSH/GSSG). Penile oxidative status was assessed by H2 O2 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. There was a significant increase in urinary H2 O2 levels in both diabetic groups. The plasma GSH/GSSG ratio was significantly augmented in late diabetes. In cavernosal tissue, H2 O2 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. 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.