Pravastatin improves the impaired nitric oxide-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in aged rats

Aging Male

Volumn 17, Issue 4, 2014, Pages 259-266

  Dalaklioglu, Selvinaz ^a   Sahin, Pinar ^a   Tasatargil, Arda ^a   Celik Ozenci, Ciler ^a  

^a AKDENIZ UNIVERSITY   (Turkey)

Author keywords

Aging; Corpus cavernosum; NADPH oxidase; Nitric oxide; Pravastatin; Rho kinase

Indexed keywords

ACETYLCHOLINE; CHOLESTEROL; ENDOTHELIAL NITRIC OXIDE SYNTHASE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; NEURONAL NITRIC OXIDE SYNTHASE; NITRIC OXIDE; PRAVASTATIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; RHO KINASE; RHO KINASE 2; TESTOSTERONE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; NITRIC OXIDE SYNTHASE;

ADULT; AGED; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; CORPUS CAVERNOSUM; DIASTOLIC BLOOD PRESSURE; DRUG EFFECT; DRUG MECHANISM; ELECTROSTIMULATION; IMMUNOHISTOCHEMISTRY; MALE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RAT; SYSTOLIC BLOOD PRESSURE; VASCULAR ENDOTHELIUM; VASODILATATION; AGING; ANIMAL; DRUG EFFECTS; PENIS; PENIS ERECTION; PHYSIOLOGY; WISTAR RAT;

AGING; ANIMALS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MALE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PENILE ERECTION; PENIS; PRAVASTATIN; RATS, WISTAR;

EID: 84911889352     PISSN: 13685538     EISSN: 14730790     Source Type: Journal    
DOI: 10.3109/13685538.2013.832194     Document Type: Article

References (49)

1. NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993;270:83-90.
2. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61.
3. Corona G, Lee DM, Forti G, et al; EMAS Study Group. Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). J Sex Med 2010;7:1362-80.
4. Carrier S, Nagaraju P, Morgan DM, et al. Age decreases nitric oxide synthase-containing nerve fibers in the rat penis. J Urol 1997; 157:1088-92.
5. Johnson JM, Bivalacqua TJ, Lagoda GA, et al. eNOS-uncoupling in age-related erectile dysfunction. Int J Impot Res 2011;23:43-8.
6. Musicki B, Kramer MF, Becker RE, Burnett AL. Age-related changes in phosphorylation of endothelial nitric oxide synthase in the rat penis. J Sex Med 2005;2:347-55; discussion 355-7.
7. Jin L, Liu T, Lagoda GA, et al. Elevated RhoA/Rho-kinase activity in the aged rat penis: mechanism for age-associated erectile dysfunction. FASEB J 2006;20:536-8.
8. Gao BH, Zhao ST, Meng FW, et al. Y-27632 improves the erectile dysfunction with ageing in SD rats through adjusting the imbalance between nNO and the Rho-kinase pathways. Andrologia 2007;39: 146-50.
9. Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation 2004;109:III39-43.
10. Nangle MR, Cotter MA, Cameron NE. Effects of rosuvastatin on nitric oxide-dependent function in aorta and corpus cavernosum of diabetic mice: relationship to cholesterol biosynthesis pathway inhibition and lipid lowering. Diabetes 2003;52:2396-402.
11. Gokce MI, Gülpinar Ö, Oztürk E, et al. Effect of atorvastatin on erectile functions in comparison with regular tadalafil use. A prospective single-blind study. Int Urol Nephrol 2012;44:683-7.
12. Trivedi D, Kirby M, Wellsted DM, et al. Can simvastatin improve erectile function and health-related quality of life in men aged 40 years with erectile dysfunction? Results of the Erectile Dysfunction and Statins Trial [ISRCTN66772971]. BJU Int 2013; 111:324-33.
13. Mastalir ET, Carvalhal GF, Portal VL. The effect of simvastatin in penile erection: a randomized, double-blind, placebo-controlled clinical trial (Simvastatin treatment for erectile dysfunction-STED TRIAL). Int J Impot Res 2011;23:242-8.
14. Davignon J, Jacob RF, Mason RP. The antioxidant effects of statins. Coron Artery Dis 2004;15:251-8.
15. Dobrucki LW, Kalinowski L, Dobrucki IT, Malinski T Statin stimulated nitric oxide release from endothelium. Med Sci Monit 2001;7:622-7.
16. Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998;97:1129-235.
17. Nakata S, Tsutsui M, Shimokawa H, et al. Statin treatment upregulates vascular neuronal nitric oxide synthase through Akt/NF-kappaB pathway. Arterioscler Thromb Vasc Biol 2007;27:92-8.
18. Ohkawara H, Ishibashi T, Saitoh S, et al. Preventive effects of pravastatin on thrombin-triggered vascular responses via Akt/eNOS and RhoA/Rac1 pathways in vivo. Cardiovasc Res 2010;88: 492-501.
19. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol 2001;21:1712-9.
20. Coelho-Filho OR, De Luca IM, Tanus-Santos JE, et al. Pravastatin reduces myocardial lesions induced by acute inhibition of nitric oxide biosynthesis in normocholesterolemic rats. Int J Cardiol 2001;79:215-21.
21. Fontaine D, Fontaine J, Dupont I, et al. Chronic hydroxymethyl-glutaryl coenzyme A reductase inhibition and endothelial function of the normocholesterolemic rat: comparison with angiotensin-converting enzyme inhibition. J Cardiovasc Pharmacol 2002;40: 172-80.
22. Kobayashi T, Matsumoto T, Kamata K. Mechanisms underlying the chronic pravastatin treatment-induced improvement in the impaired endothelium-dependent aortic relaxation seen in streptozotocin-induced diabetic rats. Br J Pharmacol 2000;131:231-8.
23. Burnett AL. Novel nitric oxide signaling mechanisms regulate the erectile response. Int J Impot Res 2004;16:S15-9.
24. Andersson KE. Erectile physiological and pathophysiological pathways involved in erectile dysfunction. J Urol 2003;170: S6-13; discussion S13-14.
25. Rajasekaran M, White S, Baquir A, Wilkes N. Rho-kinase inhibition improves erectile function in aging male Brown-Norway rats. J Androl 2005;26:182-8.
26. Numao N, Masuda H, Sakai Y, et al. Roles of attenuated neuronal nitric-oxide synthase protein expression and accelerated arginase activity in impairing neurogenic relaxation of corpus cavernosum in aged rabbits. BJU Int 2007;99:1495-9.
27. Park K, Shin JW, Oh JK, et al. Restoration of erectile capacity in normotensive aged rats by modulation of angiotensin receptor type 1. J Androl 2005;26:123-8.
28. Park CS, Ryu SD, Hwang SY. Elevation of intracavernous pressure and NO-cGMP activity by a new herbal Formula in penile tissues of aged and diabetic rats. J Ethnopharmacol 2004;94:85-92.
29. Fleming I, Busse R. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol 2003;284:R1-12.
30. Fulton D, Gratton JP, McCabe TJ, et al. Regulation of endothelium-derived nitric oxid production by the protein kinase Akt. Nature 1999;399:597-601.
31. Fulton D, Gratton JP, Sessa WC. Post-translational control of endothelial nitric oxide synthase: why isn't calcium/calmodulin enough? J Pharmacol Exp Ther 2001;299:818-24.
32. Somlyo AP, Somlyo AV. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 2003;83:1325-58.
33. Chang S, Hypolite JA, Changolkar A, et al. Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta. Int J Impot Res 2003;15:53-62.
34. Ming XF, Viswambharan H, Barandier C, et al. Rho GTPase/Rho kinase negatively regulates endothelial nitric oxide synthase phosphorylation through the inhibition of protein kinase B/Akt in human endothelial cells. Mol Cell Biol 2002;22:8467-77.
35. Bivalacqua TJ, Champion HC, Usta MF, et al. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction. Proc Natl Acad Sci USA 2004;101:9121-6.
36. Silva FH, Mónica FZ, Báu FR, et al. Superoxide anion production by NADPH oxidase plays a major role in erectile dysfunction in middle-aged rats: prevention by antioxidant therapy. J Sex Med 2013;10:960-71.
37. Mason RP, Walter MF, Day CA, Jacob RF. Intermolecular differences of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors contribute to distinct pharmacologic and pleiotropic actions. Am J Cardiol 2005;96:11F-23F.
38. Jorge PA, Osaki MR, de Almeida E. Rapid reversal of endothelial dysfunction in hypercholeterolemic rabbits treated with simvastatin and pravastatin. Clin Exp Pharmacol Physiol 1997;24:948-95.
39. Jorge PA, Almeida EA, Ozaki MR, et al. Effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, lipid peroxidation, and aortic atherosclerosis in hypercholester-olemic rabbits. Arq Bras Cardiol 2005;84:314-9.
40. Rakotoniaina Z, Guerard P, Lirussi F, et al. The protective effect of HMG-CoA reductase inhibitors against monocrotaline-induced pulmonary hypertension in the rat might not be a class effect: comparison of pravastatin and atorvastatin. Naunyn Schmiedebergs Arch Pharmacol 2006;374:195-206.
41. Guerard P, Rakotoniaina Z, Goirand F, et al. The HMG-CoA reductase inhibitor, pravastatin, prevents the development of monocrotaline-induced pulmonary hypertension in the rat through reduction of endothelial cell apoptosis and overexpression of eNOS. Naunyn Schmiedebergs Arch Pharmacol 2006;373:401-14.
42. Rao K, Liu JH. Cell apoptosis and male erectile dysfunction. Zhonghua Nan Ke Xue 2008;14:1126-9.
43. Kaneta S, Satoh K, Kano S, et al. All hydrophobic HMG-CoA reductase inhibitors induce apoptotic death in rat pulmonary vein endothelial cells. Atherosclerosis 2003;170:237-43.
44. de Sotomayor MA, Pérez-Guerrero C, Herrrera MD, et al. Improvement of age-related endothelial dysfunction by simvastatin: effect on NO and COX pathways. Br J Pharmacol 2005;146:1130-8.
45. Li C, Yang CW, Park JH, et al. Pravastatin treatment attenuates interstitial inflammation and fibrosis in a rat model of chronic cyclosporine-induced nephropathy. Am J Physiol Renal Physiol 2004;286:F46-57.
46. Laufs U, Endres M, Stagliano N, et al. Neuroprotection mediated by changes in the endotelial and cytosketketon. J Clin Invest 2000;106: 15-24.
47. Wingard CJ, Moukdar F, Prasad RY, et al. Reversal of voltage-dependent erectile responses in the Zucker obese-diabetic rat by rosuvastatin-altered RhoA/Rho-kinase signaling. J Sex Med 2009; 6:269-78.
48. Park K, Cho SY, Kim SW. Erectile response to type 5 phospho-diesterase inhibitor could be preserved with the addition of simvastatin to conventional insulin treatment in rat model of diabetes. Int J Androl 2011;34:e468-74.
49. Morelli A, Chavalmane AK, Filippi S, et al. Atorvastatin ameliorates sildenafil-induced penile erections in experimental diabetes by inhibiting diabetes-induced RhoA/Rho-kinase signaling hyper-activation. J Sex Med 2009;6:91-106.