Abstract
The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor, DA-8159, on erectile function throughout the quantitative analysis of vascular endothelial cell, smooth muscle (SM), TGF-β1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 (0, 5, 10, 20 mg/kg) was administered orally once a day to diabetic rats. After 8 weeks, immunohistochemistry and computerized image analysis were performed to quantify the percent area within the Corpora Cavernosa occupied by the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure (MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic rats showed a significant decrease in the SM and endothelial cell content, and an increase in the TGF-β1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-β1 expression level were 9.7±0.7, 4.5±0.7 and 17.9±2.1%, respectively. DA-8159 prevented reduction of SM (12.3±0.4% (5 mg/kg), 13.8±0.4% (20 mg/kg)) and endothelial cell content (5.6±0.5% (5 mg/kg), 6.3±0.6% (20 mg/kg)). Immunoreactivity of TGF-β1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8±1.2% (5 mg/kg), 9.5±1.1% (20 mg/kg)). Electrostimulation of the cavernous nerve induced significant increase in maximum ICP (62.2±13.6 mmHg in 10 mg/kg vs 37.5±17.5 mmHg in diabetic group) and area under the curve of the ratio of ICP/MAP (8891.09±1957 in 10 mg/kg vs 6315.87±2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED.
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References
Metro MJ, Broderick GA . Diabetes and vascular impotence: does insulin dependence increase the relative severity? Int J Impot Res 1999; 11: 87–89.
Vinik A, Richardson D . Erectile dysfunction in diabetes. Diab Rev 1998; 6: 16–33.
Rendell MS, Rajfer J, Wicker PA, Smith MD . Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. Sildenafil Diabetes Study Group. JAMA 1999; 281: 421–426.
Saenz De Tejada I, Anglin G, Knight JR, Emmick JT . Effects of tadalafil on erectile dysfunction in men with diabetes. Diab Care 2002; 25: 2159–2164.
Goldstein I et al. Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. Diab Care 2003; 26: 777–783.
Kang KK et al. DA-8159, a new PDE5 inhibitor, induces penile erection in conscious and acute spinal cord injured rabbits. Eur Urol 2003; 43: 689–695.
Kang KK et al. The effect of DA-8159 on corpus cavernosal smooth muscle relaxation and penile erection in diabetic rabbits. Urol Res 2004; 32: 107–111.
Rotella DP . Phosphodiesterase 5 inhibitors: current status and potential applications. Nat Rev Drug Discov 2002; 1: 674–682.
Jackson G . PDE5 inhibitors: looking beyond ED. Int J Clin Pract 2003; 57: 159–160.
McPherson MA et al. A cyclic nucleotide PDE5 inhibitor corrects defective mucin secretion in submandibular cells containing antibody directed against the cystic fibrosis transmembrane conductance regulator protein. FEBS Lett 1999; 464: 48–52.
Bortolotti M et al. Effect of sildenafil on hypertensive lower oesophageal sphincter. Eur J Clin Invest 2002; 32: 682–685.
Prasad S, Wilkinson J, Gatzoulis MA . Sildenafil in primary pulmonary hypertension. N Engl J Med 2000; 343: 1342.
Katz SD . Potential role of type 5 phosphodiesterase inhibition in the treatment of congestive heart failure. Congest Heart Fail 2003; 9: 9–15.
Kimura M et al. PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers. Hypertension 2003; 41: 1106–1110.
Schwartz EJ, Wong P, Graydon RJ . Sildenafil preserves intracorporal smooth muscle after radical retropubic prostatectomy. J Urol 2004; 171: 771–774.
De Young L, Yu D, Freeman D, Brock GB . The effect of PDE-5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model. Int J Impot Res 2003; 15: 347–354.
Leungwattanakij S et al. Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum. J Androl 2003; 24: 239–245.
Mersdorf A et al. Ultrastructural changes in impotent penile tissue: a comparison of 65 patients. J Urol 1991; 145: 749–758.
Nehra A et al. Cavernosal expandability is an erectile tissue mechanical property which predicts trabecular histology in an animal model of vasculogenic erectile dysfunction. J Urol 1998; 159: 2229–2236.
Burchardt T et al. Reduction of endothelial and smooth muscle density in the corpora cavernosa of the streptozotocin induced diabetic rat. J Urol 2000; 164: 1807–1811.
Sheenan DC, Hrapchak BB . Trichrome staining. In: Sheenan DC, Hrapchak BB (eds). Theory and Practice of Histotechnology 2nd edn. Battell Press: Richland, 1980, pp 190–191.
Richard E et al. Expression of transforming growth factor-beta1 and type IV collagen in the renal tubulointerstitium in experimental diabetes. Diabetes 1998; 47: 414–422.
Park KS et al. Diabetes mellitus induces vaginal tissue fibrosis by TGF-beta1, expression in the rat model. J Sex Marital Ther 2001; 27: 577–587.
Sattar AA, Haot J, Schulman CC, Wespes E . Comparison of anti-desmin and anti-actin staining for the computerized analysis of cavernous smooth muscle density. Br J Urol 1996; 77: 266–270.
Wespes E et al. Computerized analysis of smooth muscle fibers in potent and impotent patients. J Urol 1991; 146: 1015–1017.
Jevtich MJ, Kass M, Khawand N . Changes in the corpora cavernosa of impotent diabetics: comparing histological with clinical findings. J Urol 1985; 91: 281–285.
Rehman J et al. Diminished neurogenic but not pharmacological erections in the 2- to 3-month experimentally diabetic F-344 rat. Am J Physiol 1997; 272: 1960–1971.
Vernet D et al. Reduction of penile nitric oxide synthase in diabetic BB/WORdp (type 1) and BBZ/WORdp (type II) rats with erectile dysfunction. Endocrinol 1995; 136: 5709–5717.
Lin JS et al. Novel image analysis of corpus cavernous tissue in impotent men. Urol 2000; 55: 252–256.
Persson C et al. Correlation of altered penile ultrastructure with clinical arterial evaluation. J Urol 1989; 142: 1462–1468.
Jevtich M, Khawand NY, Vidic B . Clinical significance of ultrastructural findings in the corpus cavernosa of normal and impotent men. J Urol 1990; 143: 289–293.
Luangkhot R et al. Collagen alterations in the corpus cavernosum of men with sexual dysfunction. J Urol 1992; 148: 467–471.
Border WA, Noble NA . Transforming growth factor beta in tissue fibrosis. New Engl J Med 1994; 331: 1286–1292.
Nehra A et al. Transforming growth factor-beta1 (TGF-beta1) is sufficient to induce fibrosis of rabbit corpus cavernosum in vivo. J Urol 1999; 162: 910–915.
Quinlan DM et al. The rat as a model for the study of penile erection. J Urol 1989; 141: 656–661.
Acknowledgements
This study was supported in part by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (02-PJ2-PG4-PT01-0024).
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Ahn, G., Sohn, Y., Kang, K. et al. The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats. Int J Impot Res 17, 134–141 (2005). https://doi.org/10.1038/sj.ijir.3901295
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DOI: https://doi.org/10.1038/sj.ijir.3901295
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