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.

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