Original Article

Asian Journal of Andrology (2007) 9, 377–381; doi:10.1111/j.1745-7262.2007.00241.x

Assessment of heme oxygenase-1 (HO-1) activity in the cavernous tissues of sildenafil citrate-treated rats

M Talaat Abdel Aziz1, M Farid Al-Asmar2, Taymour Mostafa3, Hazem Atta1, Laila Rashed1, Dina Sabry1, Shedeed Ashour3 and Ahmed T Abdel Aziz1

  1. 1Molecular Biology Unit, Medical Biochemistry Department, Faculty of Medicine, Cairo University, Cairo 11553, Egypt
  2. 2Medical Biochemistry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
  3. 3Andrology Department, Faculty of Medicine, Cairo University, Cairo 11553, Egypt

Correspondence: Prof. Taymour Mostafa, Andrology Department, Faculty of Medicine, Cairo University, Cairo 11553, Egypt. Fax: +20-2363-2297. E-mail: taymour1155@link.net

Received 6 May 2006; Accepted 22 September 2006.

Top

Abstract

Aim:

 

To assess heme oxygenase-1 (HO-1) activity in the cavernous tissue of sildenafil citrate-treated rats.

Methods:

 

One hundred and ninety-two Sprague-Dawley male rats, divided into four equal groups, were investigated. Group 1, the control group, received regular animal chow; group 2 received sildenafil citrate by intragastric tube; group 3 received sildenafil and HO inhibitor (zinc protoporphyrin, ZnPP); and group 4 received sildenafil and nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester (L-NAME). Twelve rats from each group were killed after 0.5 h, 1 h, 2 h and 3 h of drug administration. Then HO-1 activity, cGMP levels and NOS enzymatic activity in the cavernous tissues were estimated.

Results:

 

In cavernous tissue, HO-1 activity, NOS enzymatic activity and cGMP concentration increased significantly in sildenafil-treated rats compared to other groups throughout the experiment. Rats receiving either HO or NOS inhibitors showed a significant decrease in these parameters. HO-1 cavernous tissue activity and NOS enzymatic activity demonstrated a positive significant correlation with cGMP levels (r = 0.646, r = 0.612 respectively; P < 0.001).

Conclusion:

 

The actions of PDE5 inhibitor sildenafil citrate in the cavernous tissue are partly mediated through the interdependent relationship between both HO-1 and NOS activities.

Keywords:

erectile dysfunction, heme oxygenase, sildenafil citrate, nitric oxide synthase, carbon monoxide

Top

References

  1. Hellstrom WJ. The molecular basis of erectile physiology: From bench to bedside. J Androl 2002; 23: S3–4. | PubMed | ISI |
  2. Seftel AD. Phosphodiesterase type 5 inhibitors: molecular pharmacology and interactions with other phosphodiesterases. Curr Pharm Des 2005; 11: 4047–58. | Article | PubMed | ISI | ChemPort |
  3. Cremers B, Bohm M. Non erectile dysfunction application of sildenafil. Herz 2003; 28: 325–33. | PubMed |
  4. Wang J, Lu S, Moenne P, Montellano OR. Interaction of nitric oxide with human heme oxygenase-1. J Biol Chem 2003; 278: 2341–7. | Article | PubMed | ChemPort |
  5. Ryter SW, Morse D, Choi AM. Carbon monoxide: to boldly go where nitric oxide has gone before. Sci STKE 2004; 2004 (230): RE6.
  6. Rodriguez F, Lamson BD, Gong W, Kemp R, Nasjletti A. Nitric oxide synthesis inhibition promotes renal production of carbon monoxide. Hypertension 2004; 43: 347–51. | Article | PubMed | ChemPort |
  7. Abdel-Aziz MT, El-Asmar MF, Mostafa T, Atta H, Abdelaziz M, Fouad H, et al. Effects of nitric oxide synthase and heme oxygenase inducers and inhibitors on molecular signaling of erectile function. Clin Biochem Nut (Japan) 2005; 37: 103–11. | Article |
  8. Paget GE, Barnes GM. Evaluation of Drug Activities. Vol. 1, Academic Press: London. 1964.
  9. Abraham NG, Lutton JD, Levere RD. Heme metabolism and erythropoiesis in abnormal iron states. Role of aminolevulinic acid synthetase and heme oxygenase. Exp Haemato 1985; 13: 833–43.
  10. Moshag H, Kok B, Huizenga JR, Jansen LM. Nitrite and nitrate determination in plasma: A critical evaluation. Clin Chem 1995; 41: 892–6. | PubMed | ISI | ChemPort |
  11. Jackson G, Gillies H, Osterloh I. Past, present and future: a 7-year update of Viagra (sildenafil citrate). Int J Clin Pract 2005; 59: 680–91. | Article | PubMed | ISI | ChemPort |
  12. Toda N, Ayajiki K, Okamura T. Nitric oxide and penile function. Pharmacol Ther 2005; 106: 233–66. | Article | PubMed | ISI | ChemPort |
  13. Vidavalur R, Penumathsa SV, Zhan L, Thirunavukkarasu M, Maulik N. Sildenafil induces angiogenic response in human coronary arteriolar endothelial cells through the expression of thioredoxin, hemeoxygenase and vascular endothelial growth factor. Vascul Pharmacol 2006; 19; 45: 91–5. | Article | ChemPort |
  14. Bivalacqua TJ, Usta MF, Champion HC, Leungwattanakij S, Dabisch PA, McNamara DB, et al. Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats. Int J Impot Res 2004; 16: 21–9. | Article | PubMed | ISI | ChemPort |
  15. Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 2006; 86: 583–650. | Article | PubMed | ISI | ChemPort |
  16. Wang R, Wang Z, Wu L. Carbon monoxide-induced vasorelaxation and the underlying mechanisms. Br J Pharmacol 1987; 121: 927–34. | Article |
  17. Hedlund P, Ny L, Anderson KE. Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase. J Urol 2000; 164: 868–75. | Article | PubMed | ISI | ChemPort |
  18. Wang J, Lu S, Moenne P, Montellano OR. Interaction of nitric oxide with human heme oxygenase-1. J Biol Chem 2003; 278: 2341–7. | Article | PubMed | ChemPort |
  19. Abraham NG, Quan S, Mieyal PA, Yang L, Burke-Wolin T, Mingone CJ, et al. Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells. Am J Physiol Lung Cell Mol Physiol 2002; 282: L1117–24. | PubMed |
  20. Di Pascoli M, Rodella L, Sacerdoti D, Bolognesi M, Turkseven S, Abraham NG. Chronic CO level has a beneficial effect on vascular relaxation in diabetes. Biochem Biophys Res Commun 2005; 340: 935–13. | Article | PubMed | ChemPort |
  21. Ahmad M, Turkseven S, Mingone CJ, Gupte SA, Wolin MS, Abraham NG. Heme oxygenase-1 gene expression increases vascular relaxation and decreases inducible nitric oxide synthase in diabetic rats. Cell Mol Biol 2005; 51: 371–6. | PubMed | ISI | ChemPort |

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

RESEARCH

Assessment of seminal plasma laminin in fertile and infertile men

Asian Journal of Andrology Original Article

Extra navigation

.

naturejobs

natureproducts


ADVERTISEMENT