title: Effect and mechanism of betaxolol and timolol on vascular relaxation in isolated rabbit ciliary artery.
abstract: OBJECTIVE
  In order to clarify the vasodilatory mechanism of betaxolol and timolol, we studied the effects of these drugs in isolated rabbit ciliary arteries.
  
  
  METHODS
  Rabbit ciliary artery specimens were mounted in a double myograph system, and betaxolol, timolol, or another agent was introduced into the organ chamber. The mechanical response of the arteries was studied using an isometric tension recording method. The intracellular free calcium concentration [Ca2+]i was also measured using fluorescence photometry.
  
  
  RESULTS
  Betaxolol and timolol induced dose-dependent relaxation in the rabbit ciliary arteries precontracted by high-K+ Krebs solution. The minimum concentrations required to cause relaxation were 10 microM of betaxolol, and 30 microM of timolol. At the maximum concentration of 1 mM, betaxolol induced almost complete relaxation of the ciliary arteries, whereas timolol induced approximately 70% relaxation. These actions were not inhibited by pretreatment with 100 microM NG-nitro-l-arginine methylester (L-NAME), a nitric oxide synthase inhibitor, or by denudation of the vascular endothelium. However, 300 microM of betaxolol or timolol decreased the [Ca2+]i of the vascular smooth muscle, an action similar to that of diltiazem, a typical L-type voltage calcium-channel blocker.
  
  
  CONCLUSIONS
  Betaxolol, a selective beta1-adrenoceptor antagonist, and timolol, a nonselective beta-adrenoceptor antagonist, both frequently used in the medical management of glaucoma, decrease [Ca2+]i by acting as Ca2+ channel blockers, thus causing relaxation of isolated rabbit ciliary artery.
authors.affiliation: Department of Ophthalmology, School of Medicine, Kitasato University, Kanagawa, Japan.|Ophthalmology Department, the Second Clinical Hospital of Jilin University, Jilin, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Orthoptics and Visual Science, School of Allied Health, Kitasato University, Kanagawa, Japan. hitoshi@kitasato-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Ophthalmology Department, the Second Clinical Hospital of Jilin University, Jilin, China.
authors.forename: Yazhen
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, School of Medicine, Kitasato University, Kanagawa, Japan.
authors.forename: Kimiya
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Ophthalmology, School of Medicine, Kitasato University, Kanagawa, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Goseki
authors.affiliation: Department of Ophthalmology, Akita University, Akita, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshitomi
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015784:Betaxolol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D019842:Ciliary Arteries / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009213:Myography; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D013999:Timolol / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D013999:Timolol; D015784:Betaxolol; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester