PURPOSE: Isopropyl unoprostone (unoprostone), a prostaglandin F(2 alpha) (PG F(2 alpha))-related compound, is widely used for treatment of glaucoma in Japan and is reported to have effects on ocular circulation. To investigate the action of this drug, we have studied the effect of unoprostone on the isolated rabbit ciliary artery. METHODS: Under microscopic observation, ciliary arteries were prepared from rabbit eyes and mounted in a myograph system. The effects of unoprostone on the isolated rabbit ciliary artery were investigated in vitro using isometric tension recordings. RESULTS: Exogenously applied PG F(2 alpha) but not unoprostone evoked contraction in the rabbit ciliary artery. After precontraction with excess-[K](o) solution, unoprostone evoked dose-dependent relaxation. The relaxation was not blocked by 10 microM/L N(G)-nitro-L-arginine methylester (L-NAME), 1 microM/L 8-37 calcitonin gene-related peptide (8-37 CGRP) or 10 microM/L indomethacin. Moreover, unoprostone could induce relaxation even in preparations without endothelium. The relaxation induced by diltiazem was greater in muscle precontracted in excess-[K](o) solution than that precontracted by 10 microM/L histamine. On the other hand, unoprostone induced a similar amplitude of relaxation in muscles precontracted by either drug. CONCLUSIONS: These results indicate that unoprostone acts directly to relax rabbit ciliary artery. The relaxation was not dependent on the endothelium and was not caused by intrinsic prostoglandins CGRP, or nitric oxide. Moreover, the relaxation was different from that caused by a Ca(2)+ antagonist. The mechanism for this relaxation is not yet determined.
PURPOSE:Isopropyl unoprostone (unoprostone), a prostaglandin F(2 alpha) (PG F(2 alpha))-related compound, is widely used for treatment of glaucoma in Japan and is reported to have effects on ocular circulation. To investigate the action of this drug, we have studied the effect of unoprostone on the isolated rabbit ciliary artery. METHODS: Under microscopic observation, ciliary arteries were prepared from rabbit eyes and mounted in a myograph system. The effects of unoprostone on the isolated rabbit ciliary artery were investigated in vitro using isometric tension recordings. RESULTS: Exogenously applied PG F(2 alpha) but not unoprostone evoked contraction in the rabbit ciliary artery. After precontraction with excess-[K](o) solution, unoprostone evoked dose-dependent relaxation. The relaxation was not blocked by 10 microM/L N(G)-nitro-L-arginine methylester (L-NAME), 1 microM/L 8-37 calcitonin gene-related peptide (8-37 CGRP) or 10 microM/L indomethacin. Moreover, unoprostone could induce relaxation even in preparations without endothelium. The relaxation induced by diltiazem was greater in muscle precontracted in excess-[K](o) solution than that precontracted by 10 microM/L histamine. On the other hand, unoprostone induced a similar amplitude of relaxation in muscles precontracted by either drug. CONCLUSIONS: These results indicate that unoprostone acts directly to relax rabbit ciliary artery. The relaxation was not dependent on the endothelium and was not caused by intrinsic prostoglandins CGRP, or nitric oxide. Moreover, the relaxation was different from that caused by a Ca(2)+ antagonist. The mechanism for this relaxation is not yet determined.