title: Sildenafil citrate for prophylaxis of nephropathy in an animal model of contrast-induced acute kidney injury.
abstract: Contrast-induced acute kidney injury (CIAKI) is one of the commonest complications associated with contrast media (CM). Although the exact etiology of CIAKI remains unclear, one hypothesis involves vasoconstriction of afferent arterioles resulting in renal ischemia. Increased renal blood flow, therefore, might represent an attractive target for the treatment of CIAKI. In this study we evaluated the protective effects of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil citrate, in a rabbit model of CIAKI. New Zealand white rabbits were used due to their susceptibility to CIAKI. To evaluate the effects of sildenafil, the drug was administered before CM infusion and repeatedly throughout the remainder of the experiment (6 mg/kg, p.o.). Animals were sacrificed after 48 hours and kidneys were prepared for histological evaluation. Intravenous administration of CM produced marked kidney injury. Serum creatinine concentrations were elevated within two hours of the infusion and remained elevated for the duration of the experiment. Histological evaluation of the kidneys revealed significant tubular necrosis. The effects of the CM were dose dependent. Treatment with sildenafil was associated with lesser degree of histological injury, attenuation in markers of acute kidney injury (48 hour creatinine 1.54±0.21 versus 4.42±1.31 mg/dl, p<0.05) and reduction in electrolyte derangement (percent change in serum K+ at 48 hours 2.55±3.80% versus 15.53±4.47%, p<0.05; serum Na+ at 48 hours -0.14±0.26% versus -1.97±1.29%, p = 0.20). The results suggest a possible role for PDE5 inhibitors in the treatment of CIAKI and warrant further evaluation to determine the exact mechanism of protection.
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: D Adam
authors.initials: DA
authors.lastname: Lauver
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: E Grant
authors.initials: EG
authors.lastname: Carey
authors.affiliation: Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Bergin
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Benedict R
authors.initials: BR
authors.lastname: Lucchesi
authors.affiliation: Department of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Hitinder S
authors.initials: HS
authors.lastname: Gurm
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D003287:Contrast Media / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011817:Rabbits; D000068677:Sildenafil Citrate / Q000627:therapeutic use*; D064804:Urological Agents / Q000627:therapeutic use
chemical_list: D003287:Contrast Media; D058986:Phosphodiesterase 5 Inhibitors; D064804:Urological Agents; D003404:Creatinine; D000068677:Sildenafil Citrate