TY - JOUR
T1 - Chronic vardenafil treatment improves erectile function via structural maintenance of penile corpora cavernosa in rats with acute arteriogenic erectile dysfunction
AU - Hotta, Yuji
AU - Hattori, Mayuko
AU - Kataoka, Tomoya
AU - Ohno, Risa
AU - Mikumo, Mayumi
AU - Maeda, Yasuhiro
AU - Kimura, Kazunori
N1 - Funding Information:
The authors thank Bayer for providing vardenafil. This study was supported by a Grant‐in‐Aid for Scientific Research (C) (No. 19590153) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
PY - 2011/3
Y1 - 2011/3
N2 - 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 (0.4mg/kg/day; VL group) or high-dose (4.0mg/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)-β1, 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-β1 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-β1 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.
AB - 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 (0.4mg/kg/day; VL group) or high-dose (4.0mg/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)-β1, 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-β1 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-β1 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.
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U2 - 10.1111/j.1743-6109.2010.02153.x
DO - 10.1111/j.1743-6109.2010.02153.x
M3 - Article
C2 - 21143425
AN - SCOPUS:79951962170
SN - 1743-6095
VL - 8
SP - 705
EP - 711
JO - Journal of Sexual Medicine
JF - Journal of Sexual Medicine
IS - 3
ER -
