title: Dorzolamide-induced relaxation of intraocular porcine ciliary arteries in vitro depends on nitric oxide and the vascular endothelium.
abstract: OBJECTIVE
  Carbonic anhydrase inhibitors (CAIs) are used to reduce aqueous production in glaucoma, which includes a direct effect on the ciliary body. However, CAIs also affect ciliary blood flow, but the mechanisms of action of CAIs on the tone of intraocular ciliary arteries supplying the ciliary body have not been studied in detail.
  
  
  METHODS
  The intraocular part of porcine ciliary arteries was isolated and mounted in a wire myograph system for isometric tension recordings. After contraction with the thromboxane analogue U46619, the vasorelaxing effect of the CAIs acetazolamide, brinzolamide and dorzolamide was studied. Subsequently, the involvement of the carbonic anhydrase reaction and nitric oxide (NO) in dorzolamide-induced vasorelaxation was characterized.
  
  
  RESULTS
  All CAIs induced relaxation of contracted ciliary arteries, but the effect of dorzolamide was most pronounced. Dorzolamide-induced relaxation was unaffected by changes in pH and CO(2), and by removal of substrates to the carbonic anhydrase enzyme, but was abolished after inhibition of NO synthase and guanylyl cyclase and after removal of the vascular endothelium.
  
  
  CONCLUSIONS
  Dorzolamide-induced vasorelaxation of ciliary arteries is independent of changes in the substances involved in the carbonic anhydrase reaction, but depends on NO and the vascular endothelium. The mechanism of action of dorzolamide in ocular disease may involve an effect on vascular tone mediated by NO.
authors: Department of Ophthalmology, Aarhus University Hospital, Aarhus C, Denmark. sidse@kringelholt.dk
authors: Sidse
authors: S
authors: Kringelholt
authors: Ulf
authors: U
authors: Simonsen
authors: Toke
authors: T
authors: Bek
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D019842:Ciliary Arteries / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007537:Isometric Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D013552:Swine; D013843:Thiazines / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D002257:Carbonic Anhydrase Inhibitors; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D013449:Sulfonamides; D013843:Thiazines; D013876:Thiophenes; D014665:Vasodilator Agents; D002245:Carbon Dioxide; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; C111827:brinzolamide; C062765:dorzolamide; D000086:Acetazolamide