ABSTRACT
INTRODUCTION: In our previous study, chronic vardenafil treatment improved erectile function soon after the end of the treatment in rats with acute arteriogenic erectile dysfunction (ED). AIM: The aim of this study is to evaluate whether the effects of chronic vardenafil treatment persist after the end of treatment using rats with acute arteriogenic ED. METHODS: Rats were randomly divided into three groups: (i) control; (ii) ligation; and (iii) vardenafil + no treatment. Rats in the ligation and vardenafil + no treatment groups underwent ligature of the bilateral internal iliac arteries to induce acute arteriogenic ED and were subsequently treated with vehicle or vardenafil (4.0 mg/kg/day), respectively, for 3 weeks. Subsequently, all rats were kept for a further 2 weeks with no treatment. Rats in the control group underwent sham surgery. MAIN OUTCOME MEASURES: Erectile function was assessed by changes in intracavernous pressure (ICP). Smooth muscle (SM)/collagen ratios in corpus cavernosum were analyzed by Masson trichrome staining. Transforming growth factor-ß1 (TGF-ß1 ) mRNA and protein levels in corpus cavernosum (CC) were, respectively, evaluated by real-time polymerase chain reaction (PCR) analysis and Western blotting analysis. RESULTS: ICP/mean arterial pressure (MAP) in the ligation group remained significantly lower than that in control group (P < 0.01). Despite no treatment for 2 weeks, ICP/MAP in the var + no treatment group remained significantly higher than that in ligation group (P < 0.05). SM/collagen ratio in the ligation group remained significantly lower when compared with the control group (P < 0.01). The ratio in the var + no treatment group remained significantly higher when compared with the ligation group at 2 weeks after the end of treatment (P < 0.05). TGF-ß(1) mRNA and protein levels did not differ among the groups. CONCLUSIONS: The effects of chronic vardenafil treatment on erectile function and penile structure persist, even after the end of treatment, in acute arteriogenic ED rats.
Subject(s)
Imidazoles/therapeutic use , Impotence, Vasculogenic/drug therapy , Phosphodiesterase 5 Inhibitors/therapeutic use , Piperazines/therapeutic use , Animals , Blotting, Western , Male , Muscle, Smooth, Vascular/drug effects , Penile Erection/drug effects , Penis/chemistry , Penis/drug effects , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction , Sulfones/therapeutic use , Transforming Growth Factor beta1/analysis , Triazines/therapeutic use , Vardenafil DihydrochlorideABSTRACT
INTRODUCTION: Chronic phosphodiesterase type 5 inhibitor treatment may be useful in reversing erectile dysfunction (ED). However, the mechanisms of this improvement remain unknown. AIM: The aim of this article was to determine the mechanisms of the improvement by chronic vardenafil treatment for acute arteriogenic ED in rats. METHODS: Eight-week-old male Wistar-ST rats were divided into four groups: sham-operated rats (Control group) and rats with acute arteriogenic ED induced by ligating bilateral internal iliac arteries (Ligation group), subsequently treated with low-dose (0.4 mg/kg/day; VL group) or high-dose (4.0 mg/kg/day; VH group) vardenafil for 20 days from 1 week after ligature. MAIN OUTCOME MEASURES: Erectile function was assessed based on changes of intracavernous pressure (ICP) followed by electrostimulation of the cavernous nerves and was evaluated by the area under the curve of ICP/area under the curve of mean arterial pressure (area of ICP/MAP). Transforming growth factor (TGF)-ß(1), vascular endothelial growth factor-A, endothelial nitric oxide synthase (eNOS), inducible NOS, and neuronal NOS mRNA expression levels in penile corpus cavernosum were determined by real-time PCR. Western blotting for TGF-ß(1) protein levels and Masson trichrome staining of penile tissues were performed in each at group 4 weeks after surgery. RESULTS: In the VH group, area of ICP/MAP was significantly improved when compared with the Ligation group (P < 0.01). The smooth muscle (SM)/collagen ratio in the VH group was significantly higher than in the Ligation group (P < 0.05), and was comparable with that in the Control group. TGF-ß(1) mRNA and protein levels in the VH group were significantly lower when compared with the Ligation group (P < 0.05). CONCLUSIONS: Chronic vardenafil administration ameliorates impairment of penile hemodynamics and maintains normal SM to collagen ratio in cavernous tissues after acute arterial injury in rats.