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

Aziz MT, Al-Asmar MF, Mostafa T, Atta H, Rashed L, Sabry D, Ashour S, Aziz AT

Molecular Biology Unit, Medical Biochemistry Department, Faculty of Medicine, Cairo University, Cairo 11553, Egypt.

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.

Published 8 May 2007 in Asian J Androl, 9(3): 377-81.
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