Early administration of phosphodiesterase 5 inhibitors after induction of diabetes in a rat model may prevent erectile dysfunction.

Abstract

The possible role of phosphodiesterase 5 inhibitors (PDE5Is) in prevention of negative effect of diabetes mellitus (DM) on erectile function is not well settled. To investigate the effect of early administration of vardenafil on erectile function, cavernosal structure, and genes expression in a rat model of DM. This experimental study was carried out atSuez Canal University's research laboratory. This study was conducted on a total of 60 adult male Albino Wistar rats, aged 60-80days and weighing an average of 200g. Rats were equally divided into six groups of 10 rats each: Group I (sham); Group II (DM with no treatment); Groups III, IV, V, and VI received vardenafil started at day 1, week 4, week 8, and week 12 after induction of DM, respectively. Functional study assessment of all groups was performed before euthanization, and then tissues were harvested for histopathological, ultrastructural, and molecular examinations. There was a significant difference of intracavernosal pressure between early (94±2.18) and late (40.5±1.94) treatment groups (p=0.011). Histopathological and ultrastructural changes of DM with no treatment and late treatment groups showed distorted cavernous architecture and extensive fibrosis. There was significant difference of smooth muscle to collagen ratio between early and late treatment groups (p=0.035). There was significant upregulation of nNOS(p=0.021) and iNOS (p=0.047) in early vs. late treatment group. The difference was insignificant in eNOS (p=0.386) or TGF-β1(p=0.149). Early treated rats with vardenafil had preserved erection and normal cavernosal structure, ultrastructure and gene expression of iNOS, nNOS, eNOS, and TGF-β1. Quantification of gene expression would improve our knowledge regarding cytokines expression and molecular background of DM-associated ED. Clinical application of this result may encourage early administration of PDE5I to prevent deleterious effects of DM on erectile function in newly diagnosed DM patients with probable uncontrolled blood glucose.