title: Dorzolamide-induced relaxation of isolated rabbit ciliary arteries mediated by inhibition of extracellular calcium influx.
abstract: OBJECTIVE
  The carbonic anhydrase inhibitor dorzolamide can increase optic nerve blood flow. The aim of the study reported here was to investigate the effect of dorzolamide on isolated rabbit ciliary arteries that supply the optic nerve.
  
  
  METHODS
  Changes in ciliary artery isometric tension and intracellular Ca(2+) concentration ([Ca(2+)]i) were recorded to elucidate the underlying pharmacologic mechanisms by which dorzolamide regulates blood flow to the optic nerve.
  
  
  RESULTS
  Dorzolamide induced concentration-dependent relaxation of rabbit ciliary arteries that had been precontracted by exposure to a high potassium (high-K) solution. Neither pretreatment with 10 µM KB-R 7943, an Na(+)/Ca(2+) exchanger inhibitor, nor alkalinization of the high-K solution had an effect on the dorzolamide-induced relaxation. Pretreatment with 100 µM N(G)-nitro-L-arginine methylester, a nitric oxide synthase inhibitor (n = 10), 10 µM indomethacin, a prostacyclin inhibitor (n = 9), or 0.1 µM iberiotoxin, an inhibitor of endothelium-derived hyperpolarizing factor (n = 7), did not change the concentration-dependent relaxation induced by dorzolamide. Incubation with 3 mM dorzolamide in a Ca(2+)-free solution did not change the transient contractions of the rabbit ciliary arteries induced by 1 µM histamine (n = 9). However, 3 mM dorzolamide significantly suppressed the increase in [Ca(2+)]i induced by the reintroduction of Ca(2+) to a calcium-free extracellular medium (P < 0.05). Furthermore, 3 mM dorzolamide significantly suppressed the [Ca(2+)]i increase induced by the high-K solution (P < 0.05).
  
  
  CONCLUSIONS
  Taken together, our results reveal a novel role for dorzolamide in relaxing the ciliary arteries. Our data support the hypothesis that the vasodilatory action of dorzolamide is mediated by inhibition of Ca(2+) entry through voltage-dependent Ca(2+) channels.
authors.affiliation: Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.|Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sawada
authors.affiliation: Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China.
authors.forename: Jizhe
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayakawa
authors.affiliation: Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Ogino
authors.affiliation: Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan. yoshitom@med.akita-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshitomi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors; D019842:Ciliary Arteries / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D015590:Fluorophotometry; D007537:Isometric Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009900:Optic Nerve / Q000098:blood supply*; D011188:Potassium / Q000008:administration & dosage; D011817:Rabbits; D013449:Sulfonamides; D013876:Thiophenes; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; D014665:Vasodilator Agents; C062765:dorzolamide; D011188:Potassium; D002118:Calcium
keywords: Calcium; Ciliary artery; Dorzolamide; Glaucoma; Vasodilation