Atorvastatin improves erectile dysfunction in patients initially irresponsive to Sildenafil by the activation of endothelial nitric oxide synthase

International Journal of Impotence Research

Volumn 25, Issue 4, 2013, Pages 143-148

  El Sisi, A A ^a   Hegazy, S K ^a   Salem, K A ^b   Abdelkawy, K S ^c  

^a Tanta University   (Egypt)

^b TANTA UNIVERSITY   (Egypt)

^c TANTA UNIVERSITY   (Egypt)

Author keywords

atorvastatin; erection; nitric oxide; sildenafil; Vitamin E

Indexed keywords

ALPHA TOCOPHEROL; ATORVASTATIN; C REACTIVE PROTEIN; ENDOTHELIAL NITRIC OXIDE SYNTHASE; GLUTATHIONE PEROXIDASE; INTERLEUKIN 6; NITRIC OXIDE; PLACEBO; SILDENAFIL; SUPEROXIDE DISMUTASE;

ADULT; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; BIOCHEMISTRY; CLINICAL STUDY; CONTROLLED STUDY; DRUG MECHANISM; ENZYME ACTIVITY; ERECTILE DYSFUNCTION; FOLLOW UP; FUNCTION TEST; HUMAN; INTERNATIONAL INDEX OF ERECTILE FUNCTION; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; RIGIDITY; TREATMENT DURATION; TREATMENT RESPONSE;

ADULT; C-REACTIVE PROTEIN; DRUG RESISTANCE; ENZYME ACTIVATION; ERECTILE DYSFUNCTION; HEPTANOIC ACIDS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INTERLEUKIN-6; MALE; MIDDLE AGED; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; PENILE ERECTION; PHOSPHODIESTERASE INHIBITORS; PIPERAZINES; PLACEBOS; PURINES; PYRROLES; SULFONES; SUPEROXIDE DISMUTASE; VITAMIN E;

EID: 84880326734     PISSN: 09559930     EISSN: 14765489     Source Type: Journal    
DOI: 10.1038/ijir.2012.46     Document Type: Article

References (50)

1. Hatzimouratidis K, Amar E, Eardleyc I, Giulianod F, Hatzichristoua D, Montorsie F et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol 2010; 57: 804-814.
2. Kendirci M, Tanriverdi O, Trost L, Hellstrom W. Management of sildenafil treatment failures. Curr Opin Urol 2006; 16: 449-459. (Pubitemid 44624580)
3. Robinson SD, Ludlam CA, Boon NA, Newby DE. Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease. Heart 2006; 92: 170-176. (Pubitemid 43131953)
4. Porst H. The future of erectile dysfunction (ED). Arch Esp Urol 2010; 63: 740-747.
5. Cohen J. The t-test for means. In: Cohen JStatistical Power Analysis for the Behavioral Sciences. 2nd Edition (Lawrence Erlbaum Associate: NewJersy, 1988, pp 19-75.
6. Dadkhah F, Hosseini S, Safarinejad M, Lashay A, Amini E. POD-09.03: Atorvastatin Improves the Response to Sildenafil in Normocholesterolemic Men with Erectile Dysfunction Not Initially Responsive to Sildenafil. Urol 2009; 74: S27-S28.
7. Paolisso G, Barbagallo M, Petrella G, Ragno E, Barbieri M, Giordano M et al. Effects of simvastatin and atorvastatin administration on insulin resistance and respiratory quotient in aged dyslipidemic non-insulin dependent diabetic patients. Atherosclerosis 2000; 150: 121-127.
8. Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001; 5: 62-71. (Pubitemid 34146173)
9. Montgomery H, Dymock J. The determination of nitrite in water. Analyst (London) 1961; 86: 414-416.
10. Nishikimi M, Appaji N, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 1972; 46: 849-854.
11. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of glutathione peroxidase. J Clin Lab Med 1967; 70: 158-169.
12. Dixon JS, Bird HA, Sitton NG, Pickup ME, Wright V. C-reactive protein in the Serial assessment of disease activity in rheumatoid arthritis. Scand J Rheum 1984; 13: 39-44. (Pubitemid 14139761)
13. Mesri M, Altieri D. Endothelial cell activation by leukocyte microparticles. J Immunol 1998; 161: 4382-4387. (Pubitemid 28469024)
14. Kleinbongard P, Schulz R, Rassaf T, Lauer T, Dejam A, Jax T et al. Red blood cells express a functional endothelial nitric oxide synthase. Blood 2006; 107: 2943-2951.
15. Chigo D, Riganti C, Gazzano E, Costamagna C, Bosia A. Cycling of NADPH by glucose 6-phosphate dehydrogenase optimizes the spectrophotometric assay of nitric oxide synthase activity in cell lysates. Nitric oxide 2006; 15: 148-153. (Pubitemid 44175883)
16. Cappelleri JC, Rosen RC. The sexual health inventory for men (SHIM): a 5-year review of research and clinical experience. Int J Impot Res 2005; 17: 307-319. (Pubitemid 41025762)
17. Wylie KR, Steward D, Walters SJ. Does vibration offer any advantage over visual stimulation studies (VSS) in the assessment of erectile capacity? Int J Impot Res 2001; 13: 329-337. (Pubitemid 34037353)
18. Herrmann HC, Levine LA, JJr Macaluso, Walsh M, Bradbury D, Schwartz S et al. Can atorvastatin improve the response to sildenafil in men with erectile dysfunction not initially responsive to sildenafil? Hypothesis and pilot trial results. J Sex Med 2006; 3: 303-308.
19. Ubrich C, Dernbach E, Zeiher A, Dimmeler S. Double-edged role of statins in angiogenesis signaling. Circ Res 2002; 90: 737-744. (Pubitemid 34640894)
20. Park JS, Kim YJ, Choi JY, Kim YN, Hong TJ, Kim DS et al. Comparative study of low doses of rosuvastatin and atorvastatin on lipid and glycemic control in patients with metabolic syndrome and hypercholesterolemia. Korean J Intern Med 2010; 25: 27-35.
21. Pennisi G, Vacante M, Russo C, Malaguarnera M. Rhabdomyolysis induced by rosuvastatin and sildenafil. South Med J 2010; 103: 1052-1054.
22. Watkins Bruner D, James J, Bryan C, Pisansky T, Rotman M, Corbett T et al. Randomized, double-blinded, placebo-controlled crossover trial of treating erectile dysfunction with sildenafil after radiotherapy and short-term androgen deprivation therapy: results of RTOG 0215. J Sex Med 2011; 8: 1228-1238.
23. Marin R, Escrig A, Abreu P, Mas M. Androgen-dependent nitric oxide release in rat penis correlates with levels of constitutive nitric oxide synthase isoenzymes. Biol Reprod 1999; 61: 1012-1016. (Pubitemid 29455639)
24. Morelli A, Filippi S, Mancina R, Luconi M, Vignozzi L, Marini M et al. Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology 2004; 146: 2253-2263. (Pubitemid 38535054)
25. Karalis DG, Ross AM, Vacari RM, Zarren H, Scott R. Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease. Am J Cardiol 2002; 89: 667-671. (Pubitemid 34230561)
26. Guo W, Zingg JM, Meydani M, Azzi A. Alpha-Tocopherol counteracts ritonavirinduced proinflammatory cytokines expression in differentiated THP-1 cells. Biofactors 2007; 31: 171-179. (Pubitemid 352789885)
27. Sadowitz B, Maier KG, Gahtan V. Basic science review: Statin therapy-Part I: The pleiotropic effects of statins in cardiovascular disease. Vasc Endovascular Surg 2010; 44: 241-251.
28. Meydani M, Lipman RD, Han SN, Wu D, Beharka A, Martin KR et al. The effect of long-term dietary supplementation with antioxidants. Ann N Y Acad Sci 1998; 854: 352-360. (Pubitemid 29022815)
29. Yetik-Anacak G, Catravas JD. Nitric oxide and the endothelium: History and impact on cardiovascular disease. Vascul Pharmacol 2006; 45: 268-276. (Pubitemid 44765289)
30. Gur S, Kadowitz PJ, Hellstrom WJ. A critical appraisal of erectile function in animal models of diabetes mellitus. Int J Androl 2009; 32: 93-114.
31. De Young L, Yu D, Freeman D, Brock GB. Effect of PDE5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model. Int J Impot Res 2003; 15: 347-354. (Pubitemid 37376940)
32. Economides PA, Khaodhiar L, Caselli A, Caballero AE, Keenan H, Bursell SE et al. The effect of vitamin E on endothelial function of micro-and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients. Diabet 2005; 54: 204-211. (Pubitemid 40105114)
33. Green D, O'Driscoll G, Blanksby B, Taylor R. Lack of effect of vitamin E administration on basal nitric oxide function in male smokers and non-smokers. Clin Sci (Lond) 1995; 89: 343-348.
34. Morelli A, Chavalmane AK, Filippi S, Fibbi B, Silvestrini E, Sarchielli E et al. Atorvastatin ameliorates sildenafil-induced penile erections in experimental diabetes by inhibiting diabetes-induced RhoA/Rho-kinase signaling hyperactivation. J Sex Med 2009; 6: 91-106.
35. Fibbi B, Morelli A, Marini M, Zhang XH, Mancina R, Vignozzi L et al. Atorvastatin but not elocalcitol increases sildenafil responsiveness in spontaneously hypertensive rats by regulating the RhoA/ROCK pathway. J Androl 2008; 29: 70-84.
36. Fö rstermann U, Sessa WC. Nitric oxide synthase: regulation and function. Eur Heart J 2011; 33: 829-837.
37. Coronel I, Arellano-Mendoza MG, del Valle-Mondragon L, Vargas-Robles H, Castorena-Torres F, Romo E et al. L-arginine and antioxidant diet supplementation partially restores nitric oxide-dependent regulation of phenylephrine renal vasoconstriction in diabetics rats. J Ren Nutr 2010; 20: 158-168.
38. Williams CA, Burk AO. Nutrient intake during an elite level three-day event competition is correlated to inflammatory markers and antioxidant status. Equine Vet J 2010; 42: 116-122.
39. Azadzoi KM, Schulman RN, Aviram M, Siroky MB. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. J Urol 2005; 174: 386-393. (Pubitemid 40825763)
40. Davignon J, Jacob RF, Mason RP. The antioxidant effects of statins. Coron Artery Dis 2004; 15: 251-258. (Pubitemid 39061608)
41. Li J, Sun YM, Wang LF, Li ZQ, Pan W, Cao HY. Comparison of effects of simvastatin versus atorvastatin on oxidative stress in patients with coronary heart disease. Clin Cardiol 2010; 33: 222-227.
42. Wang X, Quinn PJ. Vitamin E and its function in membranes. Prog Lipid Res 1999; 38: 309-336. (Pubitemid 29408248)
43. John A, Schmieder RE. Potential mechanisms of impaired endothelial function in arterial hypertension and hypercholesterolemia. Curr Hypertens Rep 2003; 5: 199-207. (Pubitemid 38914962)
44. Tousoulis D, Antoniades C, Vasiliadou C, Kourtellaris P, Koniari K, Marinou K et al. Effects of atorvastatin and vitamin C on forearm hyperaemic blood flow, asymmentrical dimethylarginine levels and the inflammatory process in patients with type 2 diabetes mellitus. Heart 2007; 93: 244-246. (Pubitemid 46180305)
45. Castro PF, Miranda R, Verdejo HE, Greig D, Gabrielli LA, Alcaino H et al. Pleiotropic effects of atorvastatin in heart failure: role in oxidative stress, inflammation, endothelial function, and exercise capacity. J Heart Lung Transplant 2008; 27: 435-441. (Pubitemid 351418248)
46. Park NY, Park SK, Lim Y. Long-term dietary antioxidant cocktail supplementation effectively reduces renal inflammation in diabetic mice. Br J Nutr 2011; 106: 1514-1521.
47. Bhattacharya S, Chakroborty P, Patra S, Basu Roy S, Kahn NN, Sinha AK. Purification and properties of insulin-activated nitric oxide synthase from human erythrocyte membranes. Arch Physiol Biochem 2001; 109: 441-449. (Pubitemid 34499186)
48. Rosanio S, Ye Y, Atar S, Rahman AM, Freeberg SY, Huang MH et al. Enhanced cardioprotection against ischemia-reperfusion injury with combining sildenafil with low-dose atorvastatin. Cardiovasc Drugs Ther 2006; 20: 27-36.
49. d'Uscio LV, Milstien S, Richardson D, Smith L, Katusic ZS. Long-term vitamin C treatment increases vascular tetrahydrobiopterin levels and nitric oxide synthase activity. Circ Res 2003; 92: 88-95. (Pubitemid 36105611)
50. Lue T, Broderick G. Evaluation and non surgical management of erectile dysfunction and periapism. In: Walsh P, Retik A, Stamey T (eds) Campbell's Urology. 7th Edition (WB Saunders Company: Philadelphia, 1998, pp 1157-1181.