Vasodilatory mechanism of unoprostone isopropyl on isolated rabbit ciliary artery

Abstract

Purpose. To clarify the vasodilatory mechanism of unoprostone isopropyl (unoprostone), a PG F2a 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, 10µM histamine or 10µM PG F2a. 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 Ca 2+ -free solution. However, SKF96365, a general Ca 2+ 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 Ca 2+ entry, possibly through capacitative Ca 2+ channels.