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Pharmacological investigation of vascular smooth muscle which affect ocular circulation.

影响眼循环的血管平滑肌的药理学研究。

基本信息

批准号：
08672032
负责人：
YOSHITOMI Takeshi
金额：
$ 0.7万
依托单位：
KITASATO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

Various anti-glaucoma agents is now available for the treatment of open-angle glaucoma. These drugs are considered to reduce intraocular pressure. Though it is generally accepted that increased intraocular pressure is a major risk factor in glaucoma, the role of the vascular factor is also considered to be important in the pathogenesis of optic nerve damage and visual field loss, especially in patients with normal tension glaucoma. The question of whether these drugs have any effect on ocular blood flow has been studied by many investigators by means of labeled microsphere method or laser speckle microcirculation analyzer. In an attempt to clarify the mechanisms involved in the effectiveness of these drugs on the ocular circulation, we have investigated the pharmacological properties and effects of these drugs on rabbit ciliary arterial smooth muscle in vitro using isometric tension recording methods.Phenyleptirine dose-dependently contracted ciliary artery smooth muscle and bunazosin … More (1muM) shifted this dose-response curve to the right. On the other hand, isoproterenol had no effect up to the concentration of 1 mM.Electrical field stimulation evoked contraction which was mediated by adrenergic nerve fibres. In addition, field stimulation also evoked relaxation when ciliary artery was pre-contracted by histamine. This relaxation was mediated by Nitric Oxide which may be released from non-adrenergic, non-cholinergic nerve terminals. Pilocarpine relaxed this muscle dose-dependently which is due to the release of NO from vascular endothelium. Betaxolol and timolol could directly relax rabbit ciliary artery in vitro in at relatively high concentrations, and relaxation is not due to NO released from the preparation. Presumably, this relaxation occurs through action similar to Ca antagonists. However, the clinical importance of this effect is not yet clarified. Carteolol had no relaxant effect in vitro. Unoprostone also relaxed this muscle, however, this relaxation is not mediated by NO, CGRP or Prostaglandins. This action was not seem to mediated by Ca antagonistic action as well. The mechanisms of relaxing action of unoprostone was not yet clear. Less

目前，各种抗青光眼药物可用于治疗开角型青光眼。这些药物被认为可以降低眼压。虽然人们普遍认为眼压升高是青光眼的主要危险因素，但血管因素在视神经损伤和视野丧失的发病机制中也被认为是重要的，特别是在正常张力型青光眼患者中。许多研究者利用标记微球法或激光散斑微循环分析仪对这些药物是否对眼血流有影响进行了研究。为了阐明这些药物对眼循环的影响机制，我们采用等长张力记录方法研究了这些药物的药理特性和对体外兔睫状动脉平滑肌的影响。苯来替林剂量依赖性收缩纤毛动脉平滑肌和布那唑嗪…More （1muM）使该剂量-反应曲线向右平移。另一方面，异丙肾上腺素在1 mm以下没有作用，电场刺激引起肾上腺素能神经纤维介导的收缩。此外，当睫状动脉被组胺预收缩时，电场刺激也能引起松弛。这种松弛是由一氧化氮介导的，一氧化氮可能从非肾上腺素能、非胆碱能神经末梢释放。匹罗卡品放松这种肌肉是剂量依赖性的，这是由于一氧化氮从血管内皮释放。倍他洛尔和噻莫洛尔在较高浓度下可直接使离体家兔纤毛动脉松弛，而松弛不是由于制剂释放的NO所致。据推测，这种松弛是通过类似钙拮抗剂的作用发生的。然而，这种作用的临床重要性尚未明确。卡替洛尔在体外无松弛作用。Unoprostone也使该肌肉松弛，然而，这种松弛不是由NO、CGRP或前列腺素介导的。这种作用似乎也不受钙拮抗作用的介导。unoprostone的舒张作用机制尚不清楚。少