Assessment of heme oxygenase-1 (HO-1) activity in the cavernous tissues of sildenafil citrate-treated rats.
- Author:
M Talaat Abdel AZIZ
1
;
M Farid AL-ASMAR
;
Taymour MOSTAFA
;
Hazem ATTA
;
Laila RASHED
;
Dina SABRY
;
Shedeed ASHOUR
;
Ahmed T Abdel AZIZ
Author Information
- Publication Type:Journal Article
- MeSH: Administration, Oral; Animals; Cyclic GMP; metabolism; Drug Interactions; Drug Therapy, Combination; Enzyme Inhibitors; pharmacology; Heme Oxygenase-1; antagonists & inhibitors; metabolism; Male; NG-Nitroarginine Methyl Ester; pharmacology; Nitric Oxide Synthase; metabolism; Penis; drug effects; enzymology; Piperazines; pharmacology; Protoporphyrins; pharmacology; Purines; pharmacology; Rats; Rats, Sprague-Dawley; Sildenafil Citrate; Sulfones; pharmacology; Vasodilator Agents; pharmacology
- From: Asian Journal of Andrology 2007;9(3):377-381
- CountryChina
- Language:English
-
Abstract:
AIMTo assess heme oxygenase-1 (HO-1) activity in the cavernous tissue of sildenafil citrate-treated rats.
METHODSOne 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.
RESULTSIn 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).
CONCLUSIONThe actions of PDE5 inhibitor sildenafil citrate in the cavernous tissue are partly mediated through the interdependent relationship between both HO-1 and NOS activities.
