Effect and mechanism of betaxolol and timolol on vascular relaxation in isolated rabbit ciliary artery.
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.
Dong
Yaru
Y
Department of Ophthalmology, School of Medicine, Kitasato University, Kanagawa, Japan.|Ophthalmology Department, the Second Clinical Hospital of Jilin University, Jilin, China.
Ishikawa
Hitoshi
H
Department of Orthoptics and Visual Science, School of Allied Health, Kitasato University, Kanagawa, Japan. hitoshi@kitasato-u.ac.jp.
Wu
Yazhen
Y
Ophthalmology Department, the Second Clinical Hospital of Jilin University, Jilin, China.
Shimizu
Kimiya
K
Department of Ophthalmology, School of Medicine, Kitasato University, Kanagawa, Japan.
Goseki
Toshiaki
T
Department of Ophthalmology, School of Medicine, Kitasato University, Kanagawa, Japan.
Yoshitomi
Takeshi
T
Department of Ophthalmology, Akita University, Akita, Japan.
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*
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