title: Calcium channel blocker nilvadipine, but not diltiazem, inhibits ocular inflammation in endotoxin-induced uveitis.
abstract: OBJECTIVE
  Calcium channel blockers (CCBs), widely used for hypertensive patients, have recently been shown to inhibit atherosclerosis by their antioxidative action. The aim of the present study was to examine whether the CCBs nilvadipine and diltiazem reduce ocular inflammation in endotoxin-induced uveitis (EIU).
  
  
  METHODS
  EIU was induced in male C57/B6 mice with a single intraperitoneal injection of lipopolysaccharide (LPS). The animals received intraperitoneal injections of either nilvadipine, diltiazem, or vehicle for 5 days before the LPS application. Twenty-four hours after EIU induction, adherent leukocytes to the retinal vasculature were counted with a concanavalin A lectin perfusion-labeling technique. The protein concentration in the aqueous humor was measured to assess blood-ocular barrier breakdown. Retinal levels of intercellular adhesion molecule (ICAM)-1 and monocyte chemotactic protein (MCP)-1 were analyzed by enzyme-linked immunosorbent assay. LPS-stimulated generation of superoxide in murine microvascular endothelial cells was examined with a nitroblue tetrazolium assay.
  
  
  RESULTS
  Compared to vehicle treatment, application of nilvadipine, but not diltiazem, led to significant suppression of EIU-associated retinal leukocyte adhesion, together with anterior-chamber protein leakage, retinal expression of ICAM-1 and MCP-1, and LPS-induced superoxide generation in vitro.
  
  
  CONCLUSIONS
  The CCB nilvadipine exercises an inhibitory effect on the pathogenesis of ocular inflammation through the suppression of inflammation-related molecules.
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. ishidasu@med.hokudai.ac.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
authors.forename: Takashi
authors.initials: T
authors.lastname: Koto
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nagai
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
mesh_terms: D000818:Animals; D018916:Blood-Aqueous Barrier / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology*; D004195:Disease Models, Animal; D004731:Endotoxins; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D007249:Inflammation / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012160:Retina / Q000378:metabolism; D012171:Retinal Vessels / Q000166:cytology; D014605:Uveitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D002121:Calcium Channel Blockers; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004731:Endotoxins; C090509:Icam1 protein, mouse; D008070:Lipopolysaccharides; C035100:nilvadipine; D018799:Intercellular Adhesion Molecule-1; C044101:endotoxin, Escherichia coli; D004110:Diltiazem; D009543:Nifedipine