Oxidative stress is believed to affect the development of diabetic-associated vasculopathy, endothelial dysfunction, and neuropathy within erectile tissue. Our hypothesis is that, given adequate concentrations of the
oxygen free radical scavenger vitamin E, enhanced levels of circulating
nitric oxide (NO) should improve erectile function with the potential for a synergistic effect with a
phosphodiesterase type 5 (
PDE5) inhibitor. Twenty adult male Sprague-Dawley
streptozotocin-induced (60 mg/kg intraperitoneally) diabetic rats were placed in 4 therapeutic groups (n = 5 per group) as follows: 1)
peanut oil only (diabetic control), 2) 20 IU of
vitamin E per day, 3) 5 mg/kg of
sildenafil per day, and 4)
vitamin E plus
sildenafil using oral gavage for 3 weeks. In addition, 5 age-matched rats served as normal nondiabetic controls (normal). Erectile function was assessed by measuring the rise in intracavernous pressure (ICP) following cavernous nerve electrostimulation. Penile tissue was evaluated for neuronal
NO synthase (nNOS), smooth muscle
alpha-actin,
nitrotyrosine, and endothelial cell integrity. Urine
nitrite and
nitrate (NOx) concentration was quantified, and
electrolytes were tested by a serum biochemistry panel. A significant decrease in ICP was recorded in the diabetic animals, with improvement measured in the animals receiving
PDE5 inhibitors either with or without
vitamin E; the controls had a pressure of 54.8 +/- 5.3 cm H2O, the
vitamin E group had a pressure of 73.5 +/- 6.6 cm H2O, the
sildenafil group had a pressure of 78.4 +/- 10.77 cm H2O, and the
vitamin E plus
sildenafil group had a pressure of 87.9 +/- 5.5 cm H2O (P <.05), compared with the normal cohorts at 103.0 +/- 4.8 cm H2O. Histoexaminations showed improved nNOS, endothelial cell, and smooth muscle cell staining in the
vitamin E plus
sildenafil group compared to the control animals. Urine NOx increased significantly in all the diabetic groups but was blunted in the
vitamin E and
vitamin E plus
sildenafil groups. A significant increase in positive staining for
nitrotyrosine was observed in the
vitamin E plus
sildenafil group.
Vitamin E enhanced the
therapeutic effect of the
PDE5 inhibitor in this study, supporting the potential use of
oxygen free radical scavengers in salvaging erectile function in diabetic patients.