| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
To clarify the vasodilatory mechanism of various antiglaucoma ophthalmic agent, we have investigated the effect of these drugs on isolated rabbit ciliary artery in vitro. Under the dissecting microscope, ciliary arteries were prepared from albino rabbit eyes and mounted in a myograph system. The effects of various agents were investigated using isometric tension recording methods. Pilocarpine administration produced a dose-dependent muscle relaxation that was abolished by treatment with L-NAME, 1μM atropine, or denudation of the endothelium. We concluded that This relaxation was dependent on the endothelium and NO synthesis. Application of betaxolol or timolol dose dependently provoked relaxation. Presumably, this relaxation occurs through action similar to Ca^<2+> antagonists. Unoprostone induced a dose-dependent relaxation in ciliary arteries that were pre-contracted with high-K solution. The relaxation does not depend on adenylyl cyclase, guanylyl cyclase, or maxi-K channels. Relaxa
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tion may be mediated by inhibition of Ca^<2+> entry, possibly through capacitative Ca^<2+> channels. Nipradilol also provoked a dose-dependent relaxation in ciliary arteries. Investigations have revealed that nipradilol relaxes rabbit ciliary artery by two different mechanisms. First, the relaxation is due to the nitric oxide produced by denitrification of nipradilol itself. Second, nipradilol may act as an a-adrenergic antagonist.
Many anti-glaucoma agents have vasodilatory effect on isolated rabbit ciliary artery These actions may explain the mechanisms of increased ocular blood flow in vivo. However, mechanisms of these drugs in relaxing ciliary artery differ from each other and are also different from that of IOP reduction. Though it is generally accepted that increased intraocular pressure is a major risk factor in glaucoma, ocular vascular perfusion is also important in the pathogenesis of optic nerve damage and visual field loss, especially in patients with normal tension glaucoma. Therefore a better understanding of the effect of various antiglaucoma agents on ocular circulation is important for optimizing their clinical use. Less
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