title: PDE5 inhibition against acute renal ischemia reperfusion injury in rats: does vardenafil offer protection?
abstract: OBJECTIVE
  To evaluate the effect of vardenafil on renal function after renal ischemia-reperfusion (IR) injury (IRI) in a rat model.
  
  
  METHODS
  Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle-treated group, (2) a vehicle pretreated-IR group, (3-6) vardenafil pretreated-IR groups in doses of 0.02, 0.2, 2 and 20 μg/kg, respectively, (7) a group of IR followed by treatment with 2 μg/kg of vardenafil. Vardenafil or vehicle solution was administered one hour before unilateral nephrectomy and the induction of 45 min of ischemia on the contralateral kidney by clamping of renal pedicle. Four hours of reperfusion were allowed after renal ischemia. Studied parameters were serum creatinine, fractional excretion of sodium (FENa), and histological evaluation of renal specimens. In addition, renal tissue cGMP levels, ERK1/2 phosphorylation as well as renal function by renal scintigraphy were also evaluated.
  
  
  RESULTS
  Administration of vardenafil before the induction of ischemia resulted in a significant reduction in creatinine and FENa levels as well as in less histological lesions observed in treated kidneys in comparison with the vehicle-treated group. The underlying mechanism of cytoprotection was cGMP depended and involved the phosphorylation of ERK proteins. Renal scintigraphy confirmed that PDE5 inhibition attenuates renal IRI.
  
  
  CONCLUSIONS
  Vardenafil attenuates renal IRI. Based on similar results from relevant studies on other PDE-5 inhibitors in renal and cardiac IRI, it can be assumed that all PDE-5 inhibitors share a common mechanism of cytoprotection.
authors.affiliation: Department of Urology, University of Patras Medical School, Rion, 26 500, Patras, Greece.
authors.forename: Iason
authors.initials: I
authors.lastname: Kyriazis
authors.forename: George C
authors.initials: GC
authors.lastname: Kagadis
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kallidonis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Georgiopoulos
authors.forename: Antonia
authors.initials: A
authors.lastname: Marazioti
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Geronasiou
authors.forename: Despοina
authors.initials: D
authors.lastname: Liourdi
authors.forename: George
authors.initials: G
authors.lastname: Loudos
authors.forename: Vasilios
authors.initials: V
authors.lastname: Schinas
authors.forename: Dimitris
authors.initials: D
authors.lastname: Apostolopoulos
authors.forename: Helen
authors.initials: H
authors.lastname: Papadaki
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Flordellis
authors.forename: George C
authors.initials: GC
authors.lastname: Nikiforidis
authors.forename: Andreas
authors.initials: A
authors.lastname: Papapetropoulos
authors.forename: Evangelos Nu
authors.initials: EN
authors.lastname: Liatsikos
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000098:blood supply* / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D023421:Models, Animal; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride
chemical_list: D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D006152:Cyclic GMP