Effect of PDE5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model.

作者: L De Young , D Yu , D Freeman , G B Brock

DOI: 10.1038/SJ.IJIR.3901026

关键词:

摘要: Phosphodiesterase (PDE) inhibitors represent an important advance in the treatment of erectile dysfunction (ED). In spite widespread use and generally good efficacy, as a class they remain ineffective 15-57% men. Specific cohorts patients with severe vascular or neurogenic basis to their ED, such diabetic men those who have undergone radical pelvic surgery, demonstrate lower response rates PDE inhibition treatment. We believe that circulating levels nitric oxide (NO) may be enhanced through delivery adequate concentrations free oxygen scavenger molecules vitamin E. Higher NO, theoretically, should produce increased penile blood flow potential for synergistic effect when combined PDE5 inhibitor. With this hypothesis mind, 20 adult male Sprague-Dawley streptozotocin-induced (60 mg/kg i.p.) rats were divided into four therapeutic groups (n=5). Group I--control animals received peanut oil, group II--vitamin E IU/day, III--sildenafil 5 mg/kg/day IV--vitamin IU/day plus sildenafil mg/kg/day, by oral gavage daily 3 weeks. Erectile function was assessed rise intracavernous pressure following cavernous nerve electrostimulation. Penile tissue harvested determine changes morphology including neuronal synthase, smooth muscle alpha-actin endothelial cell integrity. protein content activity measured. Significant increases measured receiving Immunohistochemical staining showed staining. Western blot analysis did not show significant differences between groups. However, higher recorded cohort sildenafil. Vitamin inhibitor meaningful way animal model diabetes. This study indicates means salvaging among are refractory

参考文章(49)
Tom Saldeen, Dayuan Li, Jawahar L Mehta, Differential effects of α- and γ-tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis Journal of the American College of Cardiology. ,vol. 34, pp. 1208- 1215 ,(1999) , 10.1016/S0735-1097(99)00333-2
D.K. McCulloch, I.W. Campbell, F.C. Wu, R.J. Prescott, B.F. Clarke, The prevalence of diabetic impotence. Diabetologia. ,vol. 18, pp. 279- 283 ,(1980) , 10.1007/BF00251005
Ana Escrig, Raquel Marin, Pedro Abreu, Jose Luis Gonzalez-Mora, Manuel Mas, None, Changes in Mating Behavior, Erectile Function, and Nitric Oxide Levels in Penile Corpora Cavernosa in Streptozotocin-Diabetic Rats Biology of Reproduction. ,vol. 66, pp. 185- 189 ,(2002) , 10.1095/BIOLREPROD66.1.185
T. BURCHARDT, M. BURCHARDT, J. KARDEN, R. BUTTYAN, A. SHABSIGH, A. de la TAILLE, P.Y. NG, A.G. ANASTASIADIS, R. SHABSIGH, Reduction of endothelial and smooth muscle density in the corpora cavernosa of the streptozotocin induced diabetic rat. The Journal of Urology. ,vol. 164, pp. 1807- 1811 ,(2000) , 10.1016/S0022-5347(05)67111-X
Cecil S. Thompson, Faiz H. Mumtaz, Masood A. Khan, Robert M. Wallis, Dimitri P. Mikhailidis, Robert J. Morgan, Gianni D. Angelini, Jamie Y. Jeremy, The effect of sildenafil on corpus cavernosal smooth muscle relaxation and cyclic GMP formation in the diabetic rabbit European Journal of Pharmacology. ,vol. 425, pp. 57- 64 ,(2001) , 10.1016/S0014-2999(01)01077-9
K. E. Andersson, G. Wagner, Physiology of penile erection Physiological Reviews. ,vol. 75, pp. 191- 236 ,(1995) , 10.1152/PHYSREV.1995.75.1.191
Kazi Nazrul Islam, Sridevi Devaraj, Ishwarlal Jialal, α-Tocopherol Enrichment of Monocytes Decreases Agonist-Induced Adhesion to Human Endothelial Cells Circulation. ,vol. 98, pp. 2255- 2261 ,(1998) , 10.1161/01.CIR.98.21.2255
Joong Yeol Park, Sung-Woo Ha, George L. King, The role of protein kinase C activation in the pathogenesis of diabetic vascular complications. Peritoneal Dialysis International. ,vol. 19, pp. 222- 227 ,(1999) , 10.1177/089686089901902S37
Arnold Melman, Alexandru E. Benet, The epidemiology of erectile dysfunction. Urologic Clinics of North America. ,vol. 22, pp. 699- 709 ,(1995) , 10.1016/S0094-0143(21)00690-X
W D Steers, H Padma-Nathan, P A Wicker, Efficacy and safety of oral sildenafil in the treatment of erectile dysfunction: a double-blind, placebo-controlled study of 329 patients. Sildenafil Study Group. International Journal of Clinical Practice. ,vol. 52, pp. 375- 379 ,(1998)