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

被引:27
作者
Aziz, M. Talaat Abdel
Al-Asmar, M. Farid
Mostafa, Taymour [1 ]
Atta, Hazem
Rashed, Laila
Sabry, Dina
Ashour, Shedeed
Aziz, Ahmed T. Abdel
机构
[1] Cairo Univ, Fac Med, Androl Dept, Cairo 11553, Egypt
[2] Cairo Univ, Fac Med, Dept Biochem Med, Mol Biol Unit, Cairo 11553, Egypt
[3] Ain Shams Univ, Fac Med, Dept Biochem Med, Cairo, Egypt
关键词
erectile dysfunction; heme oxygenase; sildenafil citrate; nitric oxide synthase; carbon monoxide;
D O I
10.1111/j.1745-7262.2007.00241.x
中图分类号
R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
摘要
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.
引用
收藏
页码:377 / 381
页数:5
相关论文
共 20 条
[1]  
ABDELAZIZ MT, 2005, CLIN BIOCH NUT JAPAN, V37, P103
[2]  
ABRAHAM NG, 1985, EXP HEMATOL, V13, P838
[3]   Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells [J].
Abraham, NG ;
Quan, S ;
Mieyal, PA ;
Yang, LM ;
Burke-Wolin, T ;
Mingone, CJ ;
Goodman, AI ;
Nasjletti, A ;
Wolin, MS .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2002, 283 (05) :L1117-L1124
[4]   Heme oxygenase-1 gene expression increases vascular relaxation and decreases inducible nitric oxide synthase in diabetic rats [J].
Ahmad, M ;
Turkseven, S ;
Mingone, CJ ;
Gupte, SA ;
Wolin, MS ;
Abraham, NG .
CELLULAR AND MOLECULAR BIOLOGY, 2005, 51 (04) :371-376
[5]   Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats [J].
Bivalacqua, TJ ;
Usta, MF ;
Champion, HC ;
Leungwattanakij, S ;
Dabisch, PA ;
McNamara, DB ;
Kadowitz, PJ ;
Hellstrom, WJG .
INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH, 2004, 16 (01) :21-29
[6]   Non erectile dysfunction application of sildenafil [J].
Cremers, B ;
Böhm, M .
HERZ, 2003, 28 (04) :325-333
[7]   Chronic CO levels has a beneficial effect on vascular relaxation in diabetes [J].
Di Pascoli, M ;
Rodella, L ;
Sacerdoti, D ;
Bolognesi, M ;
Turkseven, S ;
Abraham, NG .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 340 (03) :935-943
[8]   Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase [J].
Hedlund, F ;
Ny, L ;
Alm, P ;
Andersson, KE .
JOURNAL OF UROLOGY, 2000, 164 (03) :868-875
[9]  
Hellstrom WJG, 2002, J ANDROL, V23, pS3
[10]   Past, present, and future:: a 7-year update of Viagra® (sildenafil citrate) [J].
Jackson, G ;
Gillies, H ;
Osterloh, I .
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, 2005, 59 (06) :680-691