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Vasodilatory mechanism of unoprostone isopropyl on isolated rabbit ciliary artery
Takeshi Yoshitomi1, Kazutsuna Yamaji, Hitoshi Ishikawa
1Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. yoshitom@wakayama-med.ac.jp
Purpose:
To clarify the vasodilatory mechanism of unoprostone isopropyl (unoprostone), a PG F2alpha related compound used for treatment of glaucoma, we have investigated the effect of this drug and its metabolites on isolated rabbit ciliary artery in vitro.
Methods:
Under the dissecting microscope, ciliary arteries were prepared from albino rabbit eyes and mounted in a myograph system. The effects of unoprostone isopropyl and other agents were investigated using isometric tension recording methods.
Results:
Unoprostone induced a dose-dependent relaxation in ciliary arteries that were pre-contracted with high-K solution, 10 microM histamine or 10 microM PG F2alpha. Neither unoprostone metabolite M1 or M2 had a relaxant effect on the precontracted vessels. Relaxation was unaffected by inhibition of adenylyl cyclase with SQ 22536, guanylyl cyclase with ODQ, or maxi-K channels with iberiotoxin. Pretreatment with unoprostone did not affect histamine-induced transient contractions in Ca2+ -free solution. However, SKF96365, a general Ca2+ channel blocker, evoked relaxation similar to unoprostone with respect to amplitude and rate of onset.
Conclusions:
Unoprostone, but not its metabolites M1 and M2, relaxed pre-contracted rabbit ciliary artery. The mechanism of vascular smooth muscle relaxation by unoprostone differs from that of IOP reduction and does not depend on adenylyl cyclase, guanylyl cyclase, or maxi-K channels. Relaxation may be mediated by inhibition of Ca2+ entry, possibly through capacitative Ca2+ channels.
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