title: ρ-Kinase inhibition reduces early microvascular leukocyte accumulation in the rat kidney following ischemia-reperfusion injury: roles of nitric oxide and blood flow.
abstract: OBJECTIVE
  To study whether microvascular leukocyte accumulation after rat renal ischemia and reperfusion (IR) is decreased by Rho kinase inhibition, independently of effects upon nitric oxide (NO) and renal blood flow.
  
  
  METHODS
  Male Wistar rats were subjected to 60 min of ischemia by bilateral clamping and 60 min of reperfusion of the renal arteries, or a sham procedure. Haemodynamics were monitored and microsphere blood flow to the kidneys was measured. The infusion of the Rho kinase inhibitor (Y27632) was commenced before clamping and IR. The NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), was administered after the start of reperfusion whilst the dopamine-1 receptor agonist fenoldopam, a renal vasodilator, was infused during the reperfusion period. Digital imaging microscopy analysis of cryosections was done to determine leukocyte accumulation and vasodilator-stimulated phosphoprotein serine 239 phosphorylation (p-VASP ser 239), a marker of endothelial NO.
  
  
  RESULTS
  Leukocytes (60-70% neutrophils) accumulated within blood vessels in the corticomedullary junction and medulla of the kidney. Leukocyte accumulation was markedly reduced by the Rho kinase inhibitor but not by fenoldopam. However, both drugs improved renal blood flow and microvascular expression of p-VASP ser 239 in the corticomedullary junction and medulla, which were decreased following IR. L-NAME treatment of IR animals pretreated with the Rho kinase inhibitor reduced blood flow and p-VASP ser 239 expression and increased leukocyte accumulation.
  
  
  CONCLUSIONS
  Early microvascular leukocyte accumulation in the corticomedullary junction and medulla of the rat kidney after IR is ameliorated by Rho kinase inhibition. This effect is partly independent upon attenuation of decreased NO and renal blood flow.
authors.affiliation: Laboratory for Physiology, VU University Medical Center, De Boelelaan 1081, Amsterdam, The Netherlands.
authors.forename: Amanda M G
authors.initials: AM
authors.lastname: Versteilen
authors.forename: Nick
authors.initials: N
authors.lastname: Blaauw
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Maggio
authors.forename: A B Johan
authors.initials: AB
authors.lastname: Groeneveld
authors.forename: Pieter
authors.initials: P
authors.lastname: Sipkema
authors.forename: René J P
authors.initials: RJ
authors.lastname: Musters
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Tangelder
mesh_terms: D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D007668:Kidney / Q000098:blood supply / Q000201:enzymology*; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: D000577:Amides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D009569:Nitric Oxide; D054460:rho-Associated Kinases