title: The role of PDE5 inhibitors in heme oxygenase-cGMP relationship in rat cavernous tissues.
abstract: BACKGROUND
  Heme oxygenase (HO) enzyme catalyzes oxidative degradation of heme to biliverdin and carbon monoxide (CO). CO shares many properties with nitric oxide (NO) including the activation of soluble guanyl cyclase.
  
  
  OBJECTIVE
  To assess cavernous tissue HO activity and cyclic guanosine monophosphate (cGMP) levels in response to oral phosphodiesterase type 5 (PDE5) inhibitors.
  
  
  METHODS
  Seven hundred twenty male Sprague-Dawley rats, divided into six groups, were investigated. Group 1, controls; group 2 received sildenafil citrate orally; group 3 received vardenafil hydrochloride; and group 4 received tadalafil. Group 5 was subdivided into three equal subgroups, received the same dose of each drug added to the HO inhibitor, Zn protoporphyrin. Group 6 was subdivided into three equal subgroups, received the same dose of each drug added to the NO inhibitor, L-nitroarginine methylester. Eight rats from each group/subgroup were sacrificed at 0.5, 1, 2, 3, 4, 6, 18, 24, and 36 hours, respectively.
  
  
  METHODS
  HO enzyme activity assay and cGMP tissue levels in dissected rat cavernous tissues.
  
  
  RESULTS
  Both cavernous tissue HO enzyme activity and cGMP levels were increased significantly in sildenafil-, vardenafil-, and tadalafil-treated rats compared with the controls, with significant decreases after either HO or NO inhibition. Cavernous tissue HO enzyme activity and cGMP showed a positive significant correlation (r = 0.854, P < 0.001).
  
  
  CONCLUSIONS
  The effects of PDE5 inhibitors in cavernous tissue are partly mediated through HO enzyme activity.
authors.affiliation: Molecular Biology Unit, Medical Biochemistry Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
authors.forename: M Talaat Abdel
authors.initials: MT
authors.lastname: Aziz
authors.forename: Taymour
authors.initials: T
authors.lastname: Mostafa
authors.forename: Hazem
authors.initials: H
authors.lastname: Atta
authors.forename: Laila
authors.initials: L
authors.lastname: Rashed
authors.forename: Samar A
authors.initials: SA
authors.lastname: Marzouk
authors.forename: Eman M
authors.initials: EM
authors.lastname: Obaia
authors.forename: Dina
authors.initials: D
authors.lastname: Sabry
authors.forename: Amira A
authors.initials: AA
authors.lastname: Hassouna
authors.forename: Amal M
authors.initials: AM
authors.lastname: El-Shehaby
authors.forename: Ahmed T Abdel
authors.initials: AT
authors.lastname: Aziz
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010413:Penis / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology; D000068581:Tadalafil; D014227:Triazines / Q000494:pharmacology; D000069058:Vardenafil Dihydrochloride; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002243:Carbolines; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014227:Triazines; D014665:Vasodilator Agents; D000069058:Vardenafil Dihydrochloride; D000068581:Tadalafil; D000068677:Sildenafil Citrate; D006419:Heme Oxygenase (Decyclizing); D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP