title: ATP-sensitive potassium (K(ATP)) channel openers diazoxide and nicorandil lower intraocular pressure in vivo.
abstract: OBJECTIVE
  To evaluate the expression of ATP-sensitive potassium (K(ATP)) channel subunits and study the effect of K(ATP) channel openers diazoxide and nicorandil on intraocular pressure (IOP) in an in vivo mouse model.
  
  
  METHODS
  Expression of K(ATP) channel subunits in normal C57BL/6 mouse eyes was studied by immunohistochemistry and confocal microscopy. Wild-type C57BL/6 mice were treated with K(ATP) channel openers diazoxide (n = 10) and nicorandil (n = 10) for 14 days. Similar treatments with diazoxide were performed on K(ir)6.2((-/-)) mice (n = 10). IOP was recorded with a handheld tonometer 1 hour, 4 hours, and 23 hours following daily treatment. Posttreatment histology was examined by light and transmission electron microscopy.
  
  
  RESULTS
  The K(ATP) channel subunits SUR2B, K(ir)6.1, and K(ir)6.2 were identified in all tissues within mouse eyes. Treatment with diazoxide in wild-type mice decreased IOP by 21.5 ± 3.2% with an absolute IOP reduction of 3.9 ± 0.6 mm Hg (P = 0.002). Nicorandil also decreased IOP (18.9 ± 1.8%) with an absolute IOP reduction of 3.4 ± 0.4 mm Hg (P = 0.002). Treatment with diazoxide in K(ir)6.2((-/-)) mice had no effect on IOP. No morphological abnormalities were observed in diazoxide- or nicorandil-treated eyes.
  
  
  CONCLUSIONS
  K(ATP) channel openers diazoxide and nicorandil are effective regulators of IOP in mouse eyes. K(ir)6.2 appears to be a major K(ATP) channel subunit through which IOP is lowered following treatment with diazoxide.
authors.affiliation: Department of Ophthalmology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Uttio Roy
authors.initials: UR
authors.lastname: Chowdhury
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Holman
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fautsch
mesh_terms: D000818:Animals; D003981:Diazoxide / Q000494:pharmacology*; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000187:drug effects*; D054086:KATP Channels / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D023421:Models, Animal; D020108:Nicorandil / Q000494:pharmacology*; D021122:Protein Subunits / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D054086:KATP Channels; D021122:Protein Subunits; D014665:Vasodilator Agents; D020108:Nicorandil; D003981:Diazoxide
keywords: anterior segment; intraocular pressure; potassium channel