Pharmacological effect of Neuropeptides on ciliary artery smooth muscle cells

神经肽对睫状动脉平滑肌细胞的药理作用

• 批准号: 18591908
• 负责人: YOSHITOMI Takeshi
• 金额: $ 2.48万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591908/
• 关键词: Ocular circulation; anti-glaucoma agents; Tafluprost; nitric oxide; ciliary artery; vascular smooth muscle; latanoprost

To clarify the vasodilatory mechanism of various antiglaucoma ophthalmic agent, we have investigated the effect of levobunolol and prostaglandin analogs 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. The effects of the same agents on intracellular free calcium ([Ca^<2+>]I) in cultured human aortic smooth muscle cells were also studied by fluorophotometry. Levobunolol relaxed ciliary artery pre-contracted with either high-K solution, 1 μM histamine, 10 μM phenylephrine, or 100 nM endothelin-1. Inhibition of endothelial nitric oxide synthase or denudation of the endothelium did not affect this relaxation. Experimental results indicate that levobunolol may relax rabbit ciliary artery by two different mechanisms. First, the relaxation could be due to the blockade of Ca^<2+> entry thr … More ough non voltage-dependent Ca^<2+> channels. Second, lecobunolol may change the Ca^<21> sensitivity of vascular smooth muscle cells. Tafluprost induced a concentration-dependent relaxation in rabbit ciliary arteries pre-contracted with a high-K solution. Tafluprost was more potent than prostaglandin E_2 (PGE_2) or prostaglandin I_2 (PGI_2). Relaxation of rabbit ciliary artery smooth muscle by tafluprost may be due, at least in part, to inhibition of capacitative Ca^<2+> entry from the extracellular space. 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

为了阐明各种抗青光眼眼药的血管扩张机制，我们研究了左旋布诺尔和前列腺素类似物对离体兔睫状动脉的作用。在解剖显微镜下制备白化兔眼睫状动脉，并将其安装在肌图系统中。采用等距张力记录法考察了不同药剂的作用。用荧光光度法研究了这些药物对体外培养的人主动脉平滑肌细胞内游离钙（[Ca^<2+>]I）的影响。左旋布诺尔与高钾溶液、1 μM组胺、10 μM苯肾上腺素或100 nM内皮素-1一起放松睫状动脉预收缩。内皮一氧化氮合酶的抑制或内皮的剥落不影响这种松弛。实验结果表明，左苯丙洛尔可能通过两种不同的机制放松家兔纤毛动脉。首先，弛豫可能是由于Ca^<2+>通道被阻塞而导致的……更多的非电压依赖性Ca^<2+>通道。其次，莱布诺尔可能改变血管平滑肌细胞Ca^<21>的敏感性。他氟前列素诱导高钾预收缩兔纤毛动脉出现浓度依赖性松弛。他氟前列素比前列腺素e2 （PGE_2）和前列腺素I_2 （PGI_2）更有效。他氟前列素使兔纤毛动脉平滑肌松弛，至少部分原因是抑制了Ca^<2+>从细胞外空间进入。许多抗青光眼药物对离体兔睫状动脉有血管扩张作用。这些作用可以解释体内眼血流量增加的机制。然而，这些药物放松纤毛动脉的作用机制各不相同，也不同于降低IOP的作用。虽然人们普遍认为眼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，特别是在正常张力型青光眼患者中。因此，更好地了解各种抗青光眼药物对眼循环的影响对优化其临床应用具有重要意义。少

项目成果

Pharmacological vascular reactivity in isol diabetic rabbit ciliary artery

糖尿病兔睫状动脉的药理学血管反应性

• 发表时间: 2007
• 期刊: Exp Eye Res 83
• 作者: Goseki T;Ishikawa H;Nishimoto H;Mashimo K;Uga S;Yoshitomi T;Shimizu K
• 通讯作者: Shimizu K

Vasodilative Effect of Tafluprost, a New Prostaglandin F2 α Derivative, on Rabbit Ciliary Artery.

他氟前列素（一种新型前列腺素 F2 α 衍生物）对兔睫状动脉的血管舒张作用。

• 发表时间: 2007
• 作者: Yoshitomi T; Dong Y;Watabe H;Sato N;Ishikawa M.
• 通讯作者: Ishikawa M.

超音波生体顕微鏡で発見された多発性虹彩毛様体嚢種による閉塞隅角緑内障の一例

超声生物显微镜发现多发虹膜环细胞囊肿所致闭角型青光眼一例

• 发表时间: 2006
• 作者: Yoshitomi;T.;Yoshitomi T;石川誠・佐藤雅俊・前田貴美人・佐藤徳子・原宏二・池上正人・吉冨健志.;早川宏一・昆野清輝・高橋和臣・吉冨健志・山木邦比古.;佐藤徳子・渡部広史・小野省太・冨吉健志.
• 通讯作者: 佐藤徳子・渡部広史・小野省太・冨吉健志.

Current issue on glaucoma in Japan

日本青光眼的最新问题

• 发表时间: 2007
• 作者: Yoshitomi;T.;Yoshitomi T
• 通讯作者: Yoshitomi T

秋田大学におけるペーチェット病患者の検討.

秋田大学对佩塞特氏病患者的检查。

• 发表时间: 2006
• 作者: Yoshitomi;T.;Yoshitomi T;石川誠・佐藤雅俊・前田貴美人・佐藤徳子・原宏二・池上正人・吉冨健志.;早川宏一・昆野清輝・高橋和臣・吉冨健志・山木邦比古.
• 通讯作者: 早川宏一・昆野清輝・高橋和臣・吉冨健志・山木邦比古.