Erection capability is potentiated by long-term sildenafil treatment: Role of blood flow-induced endothelial nitric-oxide synthase phosphorylation

Molecular Pharmacology

Volumn 68, Issue 1, 2005, Pages 226-232

  Musicki, Biljana ^a   Champion, Hunter C ^a   Becker, Robyn E ^a   Liu, Tongyun ^a   Kramer, Melissa F ^a   Burnett, Arthur L ^a  

^a JOHNS HOPKINS HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENDOTHELIAL NITRIC OXIDE SYNTHASE; PHOSPHATASE; PHOSPHODIESTERASE V; PHOSPHOMYOSIN PHOSPHATASE; PROTEIN KINASE B; RHO KINASE; SILDENAFIL; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFECT; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; LONG TERM CARE; MALE; NONHUMAN; PENIS ERECTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SIGNAL TRANSDUCTION;

AGE FACTORS; ANIMALS; MALE; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE TYPE III; PENILE ERECTION; PENIS; PHOSPHORYLATION; PIPERAZINES; RATS; RATS, INBRED F344; REGIONAL BLOOD FLOW; TIME FACTORS;

EID: 21644482050     PISSN: 0026895X     EISSN: None     Source Type: Journal    
DOI: 10.1124/mol.104.010678     Document Type: Article

References (42)

1. Andersson KE, Gemalmaz H, Waldeck K, Chapman TN, Tuttle JB, and Steers WD (1999) The effect of sildenafil on apomorphine-evoked increases in intracavernous pressure in the awake rat. J Urol 161:1707-1712.
2. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, and Naylor AM (1998) Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 159:2164-2171.
3. Behr-Roussel D, Gorny D, Mevel K, Caisey S, Bernabe J, Burgess G, Wayman C, Alexandre L, and Giuliano F (2005) Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis. Eur Urol 47:87-91.
4. Bivalacqua TJ, Champion HC, Usta MF, Cellek S, Chitaley K, Webb RC, Lewis RL, Mills TM, Hellstrom WJ, and Kadowitz PJ (2004a) RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction. Proc Natl Acad Sci USA 101:9121-9126.
5. Bivalacqua TJ, Usta MF, Champion HC, Kadowitz PJ, and Hellstrom WJ (2003) Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease. J Androl 24:S17-S37.
6. Bivalacqua TJ, Usta MF, Champion HC, Leungwattanakij S, Dabisch PA, McNamara DB, Kadowitz PJ, and Hellstrom WJ (2004b) Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats. Int J Impot Res 16:21-29.
7. Boolell M, Allen MJ, Ballard SA Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, and Gingell C (1996) Sildenafil: an orally active type 5 cyclic CMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 8:47-52.
8. Burnett AL (1997) Nitric oxide in the penis: physiology and pathology. J Urol 157:320-324.
9. Burnett AL (2004) Novel nitric oxide signaling mechanisms regulate the erectile response. Int J Impot Res 16:S15-S19.
10. Burnett AL (2005) Vasoactive pharmacotherapy to cure erectile dysfunction: fact or fiction? Urology 65:224-230.
11. Burnett AL, Lowenstein CJ, Bredt DS, Chang TS, and Snyder SH (1992) Nitric oxide: a physiologic mediator of penile erection. Science (Wash DC) 257:401-403.
12. Champion HC, Bivalacqua TJ, Takimoto E, Kass DA, and Burnett AL (2005) Phosphodiesterase-5A dysregulation in penile erectile tissue is a mechanism of priapism. Proc Natl Acad Sci USA 102:1661-1666.
13. Chang S, Hypolite JA, Changolkar A, Wein AJ, Chacko S, and DiSanto ME (2003) Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta. Int J Impot Res 15:53-62.
14. Chitaley K, Wingard CJ, Clinton Webb R, Branam H, Stopper VS, Lewis RW, and Mills TM (2001) Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway. Nat Med 7:119-122.
15. 3H]sildenafil binding to phosphodiesterase-5 is specific, kinetically heterogeneous and stimulated by cGMP. Mol Pharmacol 63:1364-1372.
16. Corbin JD and Francis SH (1999) Cyclic GMP phosphodiesterase-5: target of sildenafil. J Biol Chem 274:13729-13732.
17. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, and Zeiher AM (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature (Lond) 399:601-605.
18. Feng J, Ito M, Ichikawa K, Isaka N, Nishikawa M, Hartshorne DJ, and Nakano T (1999) Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase. J Biol Chem 274:37385-37390.
19. Ferrini M, Magee TR, Vernet D, Rajfer J, and Gonzalez-Cadavid NF (2001) Aging-related expression of inducible nitric oxide synthase and markers of tissue damage in the rat penis. Biol Reprod 64:974-982.
20. Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K, Franke TF, Papapetropoulos A, and Sessa WC (1999) Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature (Lond) 399:597-601.
21. Garban H, Marquez D, Magee T, Moody J, Rajavashisth T, Rodriguez JA, Hung A, Vernet D, Rajfer J, and Gonzalez-Cadavid NF (1997) Cloning of rat and human inducible penile nitric oxide synthase. Application for gene therapy of erectile dysfunction. Biol Reprod 56:954-963.
22. Garban H, Vernet D, Freedman A, Rajfer J, and Gonzalez-Cadavid N (1995) Effect of aging on nitric oxide-mediated penile erection in rats. Am J Physiol 268:H467-H475.
23. Gemalmaz H, Waldeck K, Chapman TN, Tuttle JB, Steers WD, and Andersson KE (2001) In vivo and in vitro investigation of the effects of sildenafil on rat cavernous smooth muscle. J Urol 165:1010-1014.
24. Hurt KJ, Musicki B, Palese MA, Crone JK, Becker RE, Moriarity JL, Snyder SH, and Burnett AL (2002) Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection. Proc Natl Acad Sci USA 99:4061-4066.
25. Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM, and Rajfer J (1990) Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 170:843-850.
26. Lin CS, Chow S, Lau A, Tu R, and Lue TF (2002) Human PDE5A gene encodes three PDE5 isoforms from two alternate promoters. Int J Impot Res 14:15-24.
27. Lin G, Xin Z-C, Lue TF, and Lin C-S (2003) Up and down-regulation of phosphodiesterase-5 as related to tachyphylaxis and priapism. J Urol 170:S15-S18.
28. Magee TR, Ferrini M, Garban HJ, Vernet D, Mitani K, Rajfer J, and Gonzalez-Cadavid NF (2002) Gene therapy of erectile dysfunction in the rat with penile neuronal nitric oxide synthase. Biol Reprod 67:1033-1041.
29. Michell BJ, Griffiths JE, Mitchelhill KI, Rodriguez-Crespo I, Tiganis T, Bozinovski S, de Montellano PR, Kemp BE, and Pearson RB (1999) The Akt kinase signals directly to endothelial nitric oxide synthase. Curr Biol 9:845-848.
30. Mills TM, Chitaley K, Lewis RW, and Webb RC (2002) Nitric oxide inhibits RhoA/Rho-kinase signaling to cause penile erection. Eur J Pharmacol 439:173-174.
31. Ming XF, Viswambharan H, Barandier C, Ruffieux J, Kaibuchi K, Rusconi S, and Yang Z (2002) 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 22:8467-8477.
32. Mondaini N, Ponchietti R, Muir GH, Montorsi F, Di Loro F, Lombardi G, and Rizzo M (2003) Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time. Int J Impot Res 15:225-228.
33. Moreland RB, Goldstein I, and Traish A (1998) Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells. Life Sci 62:309-318.
34. Musicki B, Kramer MF, Becker RE, and Burnett AL (2005) Age-related changes in phosphorylation of endothelial nitric oxide synthase in the rat penis. J Sex Med 2:347-357.
35. Musicki B, Palese MA, Crone JK, and Burnett AL (2004) Phosphorylated endothelial nitric oxide synthase mediates vascular endothelial growth factor-induced penile erection. Biol Reprod 70:282-289.
36. Salonia A, Rigattim P, and Montorsi F (2003) (2003) Sildenafil in erectile dysfunction: a critical review. Curr Med Res Opin 19:241.
37. 2+ sensitization of contraction in vascular smooth muscle. J Biol Chem 275:21722-21729.
38. Thompson CS, Mumtaz FH, Khan MA, Wallis RM, Mikhailidis DP, Morgan RJ, Angelini GD, and Jeremy JY (2001) The effect of sildenafil on corpus cavernosal smooth muscle relaxation and cyclic GMP formation in the diabetic rabbit. Eur J Pharmacol 425:57-64.
39. Turko IV, Ballard SA, Francis SH, and Corbin JD (1999) Inhibition of cyclic GMP-binding cyclic GMP-specific phosphodiesterase (Type 5) by sildenafil and related compounds. Mol Pharmacol 56:124-130.
40. Ueno N, Iwamoto Y, Segawa N, Kinoshita M, Ueda H, and Katsuoka Y (2002) The effect of sildenafil on electrostimulation-induced erection in the rat model. Int J Impot Res 14:251-255.
41. Walker DK, Ackland MJ, James GC, Muirhead GJ, Rance DJ, Wastall P, and Wright PA (1999) Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog and man. Xenobiotica 29:297-310.
42. 2+ sensitization in erectile function. J Biol Chem 277:30614-30621.