title: Effects of alpha(2)-adrenergic agonists on lipopolysaccharide-induced aqueous flare elevation in pigmented rabbits.
abstract: OBJECTIVE
  To evaluate the effects of the alpha(2)-adrenergic agonists (clonidine, apraclonidine, and guanfacine) on lipopolysaccharide (LPS)-induced aqueous flare elevation in pigmented rabbits.
  
  
  METHODS
  Anterior uveitis was induced with an intravenous injection of LPS (0.5 microg/kg) in an ear vein. The reproducibility of experimental uveitis induced by LPS (0.5 microg/kg) was also determined. Clonidine (0.01, 0.05, 0.25, or 1%), apraclonidine (1%), or guanfacine (1%) was topically instilled in the right eye 30 and 5 minutes before and 30 minutes after LPS application (N = 6 animals, respectively). Clonidine (0.25%) was topically administered three times at 30-minute intervals from 240 or 120 minutes before, or 120 or 240 minutes after LPS application (N = 6 animals, respectively). Then 1 mg/kg of yohimbine was injected into an ear vein 30 minutes before each topical three-time instillation of clonidine 1%, apraclonidine 1% or guanfacine 1% (N = 6 animals, respectively). Aqueous flare was measured with a laser flare-cell meter. Aqueous flare elevation was expressed as the area under the curve (AUC) in arbitrary units. Rabbits received the first LPS intravenous injection, and the control values of the AUC were obtained. Three months later, the alpha(2)-agonist and the second LPS administration were given to the same animals.
  
  
  RESULTS
  The AUCs (5,184 +/- 1,255 units) after the first application of LPS were similar to those (5,033 +/- 1,290) after the second application 3 months after the first administration. Topical instillation of clonidine inhibited LPS-induced aqueous flare elevation in a dose-dependent manner (0.01-0.25%). Topical instillation of clonidine 1%, apraclonidine 1% or guanfacine 1% inhibited LPS-induced aqueous flare elevation by 98 +/- 2.0% (mean +/- SD), 86 +/- 14% and 94 +/- 5.7%, respectively. Pretreatment with intravenous yohimbine prevented the inhibitory effect on flare elevation induced by each agent.
  
  
  CONCLUSIONS
  The present findings suggested that topical instillation of some alpha(2)-agonists may have an inhibitory effect on ocular inflammation, which is mediated in part by alpha(2)-receptors.
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Hayasaka
authors.forename: S
authors.initials: S
authors.lastname: Hiraki
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: C
authors.initials: C
authors.lastname: Kadoi
authors.forename: Y
authors.initials: Y
authors.lastname: Nagaki
mesh_terms: D000287:Administration, Topical; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D019540:Area Under Curve; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D016316:Guanfacine / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D015016:Yohimbine / Q000008:administration & dosage
chemical_list: D000316:Adrenergic alpha-Agonists; D008070:Lipopolysaccharides; D009883:Ophthalmic Solutions; D015016:Yohimbine; D016316:Guanfacine; C016986:apraclonidine; D003000:Clonidine