Pharmacological effects of various ant-glaucoma agents on rabbit ciliary artery

多种抗青光眼药物对兔睫状动脉的药理作用

• 批准号: 12671719
• 负责人: YOSHITOMI Takeshi
• 金额: $ 1.98万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671719/
• 关键词: Ocular circulation; anti-glaucoma agents; unoprostone; nitric oxide; ciliary artery; vascular smooth muscle; nipradilol; 当尺性収縮記録法; 非コリン非アドレナリン神経支配; 一酸化窒素(NO); 正常眼圧緑内障

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 … More 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

为探讨抗青光眼眼用药物的扩血管作用机制，我们观察了这些药物对离体兔睫状动脉的作用。在解剖显微镜下，从白化病兔眼制备睫状动脉，并安装在肌描记系统中。使用等长张力记录方法研究各种药物的作用。毛果芸香碱给药可产生剂量依赖性的肌松作用，而L-NAME、1μM阿托品或内皮剥脱可消除这种作用。结论：这种舒张作用依赖于内皮细胞和NO的合成。应用倍他洛尔或噻吗洛尔剂量依赖性地引起松弛。据推测，这种松弛作用是通过类似于Ca^2+拮抗剂的作用发生的。在用高钾溶液预收缩的睫状动脉中，乌诺前列酮诱导剂量依赖性舒张。松弛不依赖于腺苷酸环化酶，鸟苷酸环化酶，或maxi-K通道。松弛 ...更多信息 这种作用可能是通过抑制Ca^2+内流介导的，可能是通过容量性Ca^2+通道。尼普拉地洛还引起睫状动脉的剂量依赖性舒张。研究表明，尼普拉洛通过两种不同的机制舒张兔睫状动脉。首先，松弛是由于尼普拉地洛本身的反硝化作用产生的一氧化氮。许多抗青光眼药物对离体兔眼睫状动脉有舒张作用，这些作用可能解释了在体兔眼血流增加的机制。但这些药物舒张睫状动脉的机制各不相同，与降眼压的机制也不同。虽然普遍认为眼内压升高是青光眼的主要危险因素，但眼血管灌注在视神经损伤和视野丧失的发病机制中也很重要，特别是在正常眼压性青光眼患者中。因此，更好地了解各种抗青光眼药物对眼循环的影响对于优化其临床应用具有重要意义。少

项目成果

Yamaji K, Yoshitomi T, Usui S, Ohnishi Y: "Mechanical properties of the rabbit iris smooth muscles"Vision Research. 43. 479-487 (2003)

Yamaji K、Yoshitomi T、Usui S、Ohnishi Y：“兔子虹膜平滑肌的机械特性”视觉研究。

Yoshitomi T, Yamaji K, Ishikawa H Ohnishi Y: "Vasodilatory effects of nipradilol, an a-and Β adrenergic blocker with nitric oxide releasing action, in rabbit ciliary artery.."Exp. Eye Res. 75. 669-676 (2002)

Yoshitomi T、Yamaji K、Ishikawa H Ohnishi Y：“尼普地洛（一种具有一氧化氮释放作用的 α-和 β 肾上腺素能阻滞剂）对兔睫状动脉的血管舒张作用。”Exp. 75. 669-676 (2002)

Hayashi-Morimoto R,Yoshitomi T,Ishikawa H,Hayashi E and Sato Y: "Effect of βantagonists on mechanical properties in rabbit ciliary artery"Graefe's Arch Clin Exp Ophthalmol. 237. 661-667 (1999)

Hayashi-Morimoto R、Yoshitomi T、Ishikawa H、Hayashi E 和 Sato Y：“β 拮抗剂对兔睫状动脉机械性能的影响”Graefes Arch Clin Exp Ophamol. 237. 661-667 (1999)

Yoshitomi T, Yamaji K, Ishikawa H, Ohnishi Y: "Effect of latanoprost, prostaglandin F2a and nipradilol on isolated bovine ciliary muscle"Jpn J Ophthalmol. 46. 401-403 (2002)

Yoshitomi T、Yamaji K、Ishikawa H、Ohnishi Y：“拉坦前列素、前列腺素 F2a 和尼普地洛对离体牛睫状肌的影响”Jpn J Ophamol。

Yoshitomi, T, Ishikawa, H. and Hayashi, E.: "Pharmacological effects of pilocarpine on rabbit ciliary artery"Curr Eye Res. 20z. 254-259 (2000)

Yoshitomi，T，Ishikawa，H. 和 Hayashi，E.：“毛果芸香碱对兔睫状动脉的药理学作用”Curr Eye Res。