title: The ATP-sensitive potassium channel blocker glibenclamide prevents renal ischemia/reperfusion injury in rats.
abstract: BACKGROUND
  Renal ischemia/reperfusion (I/R) is a complex neutrophil-mediated syndrome. Adenosine-triphosphate (ATP)-sensitive potassium (K(ATP)) channels are involved in neutrophil migration in vivo. In the present study, we have investigated the effects of glibenclamide, a K(ATP) channel blocker, in renal I/R injury in rats.
  
  
  METHODS
  The left kidney of the rats was excised through a flank incision and ischemia was performed in the contralateral kidney by total interruption of renal artery flow for 45 minutes. Renal perfusion was reestablished, and the kidney and lungs were removed for analysis of vascular permeability, neutrophil accumulation, and content of cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-10] 4 and 24 hours later. Renal function was assessed by measuring creatinine, Na(+), and K(+) levels in the plasma and by determination of creatinine clearance. Drugs were administered subcutaneously after the onset of ischemia.
  
  
  RESULTS
  Reperfusion of the ischemic kidney induced local (kidney) and remote (lung) inflammatory injury and marked renal dysfunction. Glibenclamide (20 mg/kg) significantly inhibited the reperfusion-associated increase in vascular permeability, neutrophil accumulation, increase in TNF-alpha levels and nuclear factor-kappaB (NF-kappaB) translocation. These inhibitory effects were noticed in the kidney and lungs. Moreover, glibenclamide markedly ameliorated the renal dysfunction at 4 and 24 hours.
  
  
  CONCLUSIONS
  Treatment with glibenclamide is associated with inhibition of neutrophil recruitment and amelioration of renal dysfunction following renal I/R. Glibenclamide may have a therapeutic role in the treatment of renal I/R injury, such as after renal transplantation.
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas-Universidade Federal de Minas Gerais, Brazil.
authors.forename: Kenia
authors.initials: K
authors.lastname: Pompermayer
authors.forename: Danielle G
authors.initials: DG
authors.lastname: Souza
authors.forename: Giovanna G
authors.initials: GG
authors.lastname: Lara
authors.forename: Kátia D
authors.initials: KD
authors.lastname: Silveira
authors.forename: Geovanni D
authors.initials: GD
authors.lastname: Cassali
authors.forename: Anderson A
authors.initials: AA
authors.lastname: Andrade
authors.forename: Cláudio A
authors.initials: CA
authors.lastname: Bonjardim
authors.forename: Kátia T
authors.initials: KT
authors.lastname: Passaglio
authors.forename: Jamil
authors.initials: J
authors.lastname: Assreuy
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Maria Aparecida R
authors.initials: MA
authors.lastname: Vieira
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D005905:Glyburide / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014409:Tumor Necrosis Factor-alpha; C117780:mitochondrial K(ATP) channel; D016753:Interleukin-10; D000255:Adenosine Triphosphate; D003981:Diazoxide; D005905:Glyburide