Relaxing effect and mechanism of tafluprost on isolated rabbit ciliary arteries.
Our objective was to determine if tafluprost, a newly synthesized antiglaucoma drug, can relax precontracted rabbit ciliary arteries, and if so, to elucidate the underlying mechanism. We used isometric tension recordings of smooth muscle contractions and fluorescence photometry to monitor the change of intracellular free calcium concentration ([Ca(2+)](i)) in isolated rabbit ciliary artery segments. Tafluprost induced a concentration-dependent relaxation in rabbit ciliary arteries precontracted with a high-K solution. The amplitude of relaxation induced by tafluprost was unchanged by 100 microM L-NAME, 10 microM indomethacin, denudation of vascular endothelium, 30 microM thapsigargin, or 100 microM ouabain. In Ca(2+)-free solution, 30 microM tafluprost did not decrease the amplitude of contraction induced by 1 microM histamine or the amplitude of the [Ca(2+)](i) increase induced by 10 microM histamine. The mechanism of tafluprost-induced relaxation was different from diltiazem, a voltage-dependent Ca(2+) channel blocker. However, in thapsigargin-pretreated preparations incubated in Ca(2+)-free solution, tafluprost attenuated the capacitative increase of [Ca(2+)](i) upon Ca(2+) reintroduction to the extracellular medium. Thus, we conclude that tafluprost relaxed isolated rabbit ciliary artery segments precontracted with a high-K solution. The relaxing mechanism was not dependent on endothelial-derived factors, and not affected by the intracellular Ca(2+) cycles or the Ca(2+) extrusion component of the extracellular Ca(2+) cycles. Relaxation of rabbit ciliary artery smooth muscle by tafluprost may be due, at least in part, to inhibition of capacitative Ca(2+) entry from the extracellular space.
Dong
Yaru
Y
Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
Watabe
Hiroshi
H
Su
Guanfang
G
Ishikawa
Hitoshi
H
Sato
Noriko
N
Yoshitomi
Takeshi
T
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D019842:Ciliary Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology*; D011817:Rabbits; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
C485334:(5Z)-7-((1R,2R, 3R,5S)-2-((1E)-3,3-difluoro-4-phenoxy -1-butenyl)-3,5-dihydroxycyclopentyl)-5-heptenoic acid; D011460:Prostaglandins F; D014665:Vasodilator Agents; C485333:tafluprost; D006632:Histamine; D004110:Diltiazem; D002118:Calcium