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


CONCLUSIONS
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.
Aziz
M Talaat Abdel
MT
Molecular Biology Unit, Medical Biochemistry Department, Faculty of Medicine, Cairo University, Cairo 11553, Egypt.
Al-Asmar
M Farid
MF
Mostafa
Taymour
T
Atta
Hazem
H
Rashed
Laila
L
Sabry
Dina
D
Ashour
Shedeed
S
Aziz
Ahmed T Abdel
AT
D000284:Administration, Oral; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010413:Penis / Q000187:drug effects* / Q000201:enzymology; D010879:Piperazines / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010879:Piperazines; D011524:Protoporphyrins; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; C017803:zinc protoporphyrin; D000068677:Sildenafil Citrate; D019001:Nitric Oxide Synthase; D051547:Heme Oxygenase-1; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester