Sildenafil promotes eNOS activation and inhibits NADPH oxidase in the transgenic sickle cell mouse penis

Journal of Sexual Medicine

Volumn 11, Issue 2, 2014, Pages 424-430

  Musicki, Biljana ^a   Bivalacqua, Trinity J ^a   Champion, Hunter C ^b   Burnett, Arthur L ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

4 HNE; AKT; eNOS Phosphorylation; HSP90; Oxidative Stress

Indexed keywords

4 HYDROXYNONENAL; ENDOTHELIAL NITRIC OXIDE SYNTHASE; HEAT SHOCK PROTEIN 90; PROTEIN KINASE B; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; SILDENAFIL; 4-HYDROXY-2-NONENAL; ALDEHYDE; NITRIC OXIDE; NOS3 PROTEIN, MOUSE; PHOSPHODIESTERASE V INHIBITOR; PIPERAZINE DERIVATIVE; PURINE DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SULFONE; SUPEROXIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; MOUSE; NONHUMAN; OXIDATIVE STRESS; PENIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; SAD MOUSE; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE; 4-HNE; AKT; ANIMAL; BIOSYNTHESIS; DRUG ANTAGONISM; DRUG EFFECT; ENOS PHOSPHORYLATION; ENZYMOLOGY; GENETICS; HSP90; MALE; METABOLISM; OXIDATION REDUCTION REACTION; PHOSPHORYLATION; PRIAPISM; SICKLE CELL ANEMIA; VASCULARIZATION;

4-HNE; AKT; ENOS PHOSPHORYLATION; HSP90; OXIDATIVE STRESS;

ALDEHYDES; ANEMIA, SICKLE CELL; ANIMALS; MALE; MICE; MICE, TRANSGENIC; NADPH OXIDASE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; OXIDATION-REDUCTION; OXIDATIVE STRESS; PENIS; PHOSPHODIESTERASE 5 INHIBITORS; PHOSPHORYLATION; PIPERAZINES; PRIAPISM; PURINES; SULFONES; SUPEROXIDES;

EID: 84903187682     PISSN: 17436095     EISSN: 17436109     Source Type: Journal    
DOI: 10.1111/jsm.12391     Document Type: Article

References (45)

1. Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT. Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. Am J Hematol 2009;84:618-625.
2. Wood KC, Hsu LL, Gladwin MT. Sickle cell disease vasculopathy: A state of nitric oxide resistance. Free Radic Biol Med 2008;44:1506-1528.
3. Hoppe CC. Novel therapies targeting the endothelium in sickle cell disease. Hemoglobin 2011;35:530-546.
4. Hsu LL, Champion HC, Campbell-Lee SA, Bivalacqua TJ, Manci EA, Diwan BA, Schimel DM, Cochard AE, Wang X, Schechter AN, Noguchi CT, Gladwin MT. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 2007;109:3088-3098.
5. Champion HC, Bivalacqua TJ, Takimoto E, Kass DA, Burnett AL. Phosphodiesterase-5A dysregulation in penile erectile tissue is a mechanism of priapism. Proc Natl Acad Sci U S A 2005;102:1661-1666.
6. Kato GJ, Taylor JG 6th. Pleiotropic effects of intravascular haemolysis on vascular homeostasis. Br J Haematol 2010;148:690-701.
7. Pritchard KA Jr, Ou J, Ou Z, Shi Y, Franciosi JP, Signorino P, Kaul S, Ackland-Berglund C, Witte K, Holzhauer S, Mohandas N, Guice KS, Oldham KT, Hillery CA. Hypoxia-induced acute lung injury in murine models of sickle cell disease. Am J Physiol Lung Cell Mol Physiol 2004;286:L705-714.
8. Wood KC, Hebbel RP, Granger DN. Endothelial cell NADPH oxidase mediates the cerebral microvascular dysfunction in sickle cell transgenic mice. FASEB J 2005;19:989-991.
9. Wood KC, Hebbel RP, Lefer DJ, Granger DN. Critical role of endothelial cell-derived nitric oxide synthase in sickle cell disease-induced microvascular dysfunction. Free Radic Biol Med 2006;40:1443-1453.
10. Broderick GA. Priapism and sickle-cell anemia: Diagnosis and nonsurgical therapy. J Sex Med 2012;9:88-103.
11. Burnett AL, Bivalacqua TJ, Champion HC, Musicki B. Long-term oral phosphodiesterase 5 inhibitor therapy alleviates recurrent priapism. Urology 2006;67:1043-1048.
12. Burnett AL, Bivalacqua TJ, Champion HC, Musicki B. Feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism. J Sex Med 2006;3:1077-1084.
13. Burnett AL, Bivalacqua TJ. Priapism: Current principles and practice. Urol Clin North Am 2007;34:631-642.
14. Musicki B, Champion HC, Hsu LL, Bivalacqua TJ, Burnett AL. Posttranslational inactivation of endothelial nitric oxide synthase in the transgenic sickle cell mouse penis. J Sex Med 2011;8:419-426.
15. Lagoda G, Sezen SF, Cabrini MR, Musicki B, Burnett AL. Molecular analysis of erection regulatory factors in sickle cell disease associated priapism in the human penis. J Urol 2013;189:762-768.
16. Bivalacqua TJ, Musicki B, Hsu LL, Berkowitz DE, Champion HC, Burnett AL. Sildenafil citrate-restored eNOS and PDE5 regulation in sickle cell mouse penis prevents priapism via control of oxidative/nitrosative stress. PLoS ONE 2013;8:e68028.
17. Kanika ND, Melman A, Davies KP. Experimental priapism is associated with increased oxidative stress and activation of protein degradation pathways in corporal tissue. Int J Impot Res 2010;22:363-373.
18. Musicki B, Liu T, Sezen SF, Burnett AL. Targeting NADPH oxidase decreases oxidative stress in the transgenic sickle cell mouse penis. J Sex Med 2012;9:1980-1987.
19. Bivalacqua TJ, Musicki B, Hsu LL, Gladwin MT, Burnett AL, Champion HC. Establishment of a transgenic sickle-cell mouse model to study the pathophysiology of priapism. J Sex Med 2009;6:2494-2504.
20. Claudino MA, Franco-Penteado CF, Corat MA, Gimenes AP, Passos LA, Antunes E, Costa FF. Increased cavernosal relaxations in sickle cell mice priapism are associated with alterations in the NO-cGMP signaling pathway. J Sex Med 2009;6:2187-2196.
21. Bivalacqua TJ, Ross AE, Strong TD, Gebska MA, Musicki B, Champion HC, Burnett AL. Attenuated RhoA/Rho-kinase signaling in penis of transgenic sickle cell mice. Urology 2010;76:510.e7-5112.
22. Mi T, Abbasi S, Zhang H, Uray K, Chunn JL, Xia LW, Molina JG, Weisbrodt NW, Kellems RE, Blackburn MR, Xia Y. Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling. J Clin Invest 2008;118:1491-1501.
23. Wen J, Jiang X, Dai Y, Zhang Y, Tang Y, Sun H, Mi T, Phatarpekar PV, Kellems RE, Blackburn MR, Xia Y. Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A2B adenosine receptor signaling. FASEB J 2010;24:740-749.
24. Kanika ND, Tar M, Tong Y, Kuppam DS, Melman A, Davies KP. The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway. Am J Physiol Cell Physiol 2009;297:C916-927.
25. Pászty C, Brion CM, Manci E, Witkowska HE, Stevens ME, Mohandas N, Rubin EM. Transgenic knockout mice with exclusively human sickle hemoglobin and sickle cell disease. Science 1997;278:876-878.
26. Bivalacqua TJ, Sussan TE, Gebska MA, Strong TD, Berkowitz DE, Biswal S, Burnett AL, Champion HC. Sildenafil inhibits superoxide formation and prevents endothelial dysfunction in a mouse model of secondhand smoke induced erectile dysfunction. J Urol 2009;181:899-906.
27. Hurt KJ, Musicki B, Palese MA, Crone JC, Becker RE, Moriaruty JL, Snyder SH, Burnett AL. Akt-dependent phosphorylation of endothelial nitric oxide synthase mediated penile erection. Proc Natl Acad Sci U S A 2002;99:4061-4066.
28. Milano G, Bianciardi P, Rochemont V, Vassalli G, Segesser LK, Corno AF, Guazzi M, Samaja M. Phosphodiesterase-5 inhibition mimics intermittent reoxygenation and improves cardioprotection in the hypoxic myocardium. PLoS ONE 2011;6:e27910.
29. Musicki B, Champion HC, Becker RE, Liu T, Kramer MF, Burnett AL. Erection capability is potentiated by long-term sildenafil treatment: Role of blood flow-induced endothelial nitric-oxide synthase phosphorylation. Mol Pharmacol 2005;68:226-232.
30. Fleming I. Molecular mechanisms underlying the activation of eNOS. Pflugers Arch 2010;459:793-806.
31. Herranz B, Marquez S, Guijarro B, Aracil E, Aicart-Ramos C, Rodriguez-Crespo I, Serrano I, Rodríguez-Puyol M, Zaragoza C, Saura M. Integrin-linked kinase regulates vasomotor function by preventing endothelial nitric oxide synthase uncoupling: Role in atherosclerosis. Circ Res 2012;110:439-449.
32. Boo YC, Jo H. Flow-dependent regulation of endothelial nitric oxide synthase: Role of protein kinases. Am J Physiol Cell Physiol 2003;285:C499-508.
33. Mondaini N, Ponchietti R, Muir GH, Montorsi F, Di Loro F, Lombardi G, Rizzo M. Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time. Int J Impot Res 2003;15:225-228.
34. Behr-Roussel D, Oudot A, Caisey S, Coz OL, Gorny D, Bernabé J, Wayman C, Alexandre L, Giuliano FA. Daily treatment with sildenafil reverses endothelial dysfunction and oxidative stress in an animal model of insulin resistance. Eur Urol 2008;53:1272-1280.
35. Behr-Roussel D, Oudot A, Compagnie S, Gorny D, Le Coz O, Bernabe J, Wayman C, Alexandre L, Giuliano F. Impact of a long-term sildenafil treatment on pressor response in conscious rats with insulin resistance and hypertriglyceridemia. Am J Hypertens 2008;21:1258-1263.
36. Oudot A, Behr-Roussel D, Le Coz O, Poirier S, Bernabe J, Alexandre L, Giuliano F. How does chronic sildenafil prevent vascular oxidative stress in insulin-resistant rats? J Sex Med 2010;7:79-88.
37. Ebrahimi F, Shafaroodi H, Asadi S, Nezami BG, Ghasemi M, Rahimpour S, Hashemi M, Doostar Y, Dehpour AR. Sildenafil decreased cardiac cell apoptosis in diabetic mice: Reduction of oxidative stress as a possible mechanism. Can J Physiol Pharmacol 2009;87:556-564.
38. Yaguas K, Bautista R, Quiroz Y, Ferrebuz A, Pons H, Franco M, Vaziri ND, Rodriguez-Iturbe B. Chronic sildenafil treatment corrects endothelial dysfunction and improves hypertension. Am J Nephrol 2010;31:283-291.
39. Schafer A, Fraccarollo D, Pfortsch S, Flierl U, Vogt C, Pfrang J, Kobsar A, Renné A, Eigenthaler M, Ertl G, Bauersachs J. Improvement of vascular function by acute and chronic treatment with the PDE-5 inhibitor sildenafil in experimental diabetes mellitus. Br J Pharmacol 2008;153:886-893.
40. Luo L, Dai DZ, Cheng YS, Zhang Q, Yuan WJ, Dai Y. Sildenafil improves diabetic vascular activity through suppressing endothelin receptor A, iNOS and NADPH oxidase which is comparable with the endothelin receptor antagonist CPU0213 in STZ-injected rats. J Pharm Pharmacol 2011;63:943-951.
41. Helmy MM, Senbel AM. Evaluation of vitamin E in the treatment of erectile dysfunction in aged rats. Life Sci 2012;90:489-494.
42. Mostafa T, Rashed L, Kotb K, Taymour M. Effect of testosterone and frequent low-dose sildenafil/tadalafil on cavernous tissue oxidative stress of aged diabetic rats. Andrologia 2012;44:411-415.
43. Selemidis S, Dusting GJ, Peshavariya H, Kemp-Harper BK, Drummond GR. Nitric oxide suppresses NADPH oxidase-dependent superoxide production by S-nitrosylation in human endothelial cells. Cardiovasc Res 2007;75:349-358.
44. Qian J, Chen F, Kovalenkov Y, Pandey D, Moseley MA, Foster MW, Black SM, Venema RC, Stepp DW, Fulton DJ. Nitric oxide reduces NADPH oxidase 5 (Nox5) activity by reversible S-nitrosylation. Free Radic Biol Med 2012;52:1806-1819.
45. Duerrschmidt N, Stielow C, Muller G, Pagano PJ, Morawietz H. NO-mediated regulation of NAD(P)H oxidase by laminar shear stress in human endothelial cells. J Physiol 2006;576:557-567.