ADRENERGIC CONTROL OF OCULAR BLOOD FLOW

肾上腺素对眼血流的控制

• 批准号: 2162953
• 负责人: MICHAEL C KOSS
• 金额: $ 8.14万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-01-01 至 1995-12-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2162953
• 关键词: adrenergic agents; alpha adrenergic receptor; analog; atropine; azepines; beta adrenergic receptor; blood flow measurement; blood pressure; cardiovascular function; cats; clonidine; epinephrine; eye circulation; eye pharmacology; hexamethonium compound; intraocular pressure; isoproterenol; methoxamine; muscarinic receptor; neurophysiology; neurotransmitter receptor; norepinephrine; phentolamine; phenylephrine; prazosin; propranolol; rauwolfia alkaloid; sympathetic nervous system; ultrasound blood flow measurement; vasoactive agent

The overall purpose of this research project is to use newly available technology to study the physiology and pharmacology of blood flow in specific areas of the eye. Special emphasis will be on the role of the sympathetic nervous system in ocular vascular control and on the effects of adrenergic drugs. Previous methodologies, such as microsphere and various washout techniques, are non-continuous and are limited to steady-state flow conditions. The best o f these only produces a "snapshot" of ocular blood flow at one point in time. We will utilize laser-Doppler flowmetry to measure blood flow from the surface of the eye at the limbus (anterior segment) and at the equator (choroidal flow). A newly developed sensitive transit-time ultrasonic flowmeter will be used to directly measure blood flow from one of the two arteries supplying blood to the front of the eye (long posterior ciliary artery). Both of these methodologies provide a continuous, high-frequency response. Laser-Doppler flowmetry has a high degree spatial resolution, whereas ultrasonic flowmetry will produce more global flow of measurements. Using these techniques, determination of the effects of altered perfusion pressures on regional flow will be determined by experimentally increasing or decreasing both intra-ocular pressure and systemic blood pressure. The degree of regional autoregulation and the role of sympathetic neural input will be determined. Adrenergic drugs (both stimulants and blockers) will be used to systematically define the presence of, and relative roles of adrenergic receptor subtypes in these regional vascular beds. In recent years it has become increasingly clear that disruption of normal circulatory function in the eye may directly cause or exacerbate the pathophysiology of such diverse condition as glaucoma, various retinopathies and macular degeneration. In addition, most of the drugs currently used, or proposed for use, in the treatment of glaucoma have pronounced effects on ocular blood vessels. It is hoped that information gained from this research project will enhance our understanding of ocular physiology and pharmacology in general. More specifically, these results should expand our knowledge of specific adrenergic subtypes in these vascular beds and should prove helpful in the design of new therapeutic agents with greater receptor specificity and fewer untoward side effects.

该研究项目的总体目的是利用新近可用的 研究血液流动的生理学和药理学的技术 眼睛的特定区域。 将特别强调 交感神经系统对眼血管的控制及其影响 肾上腺素能药物。 以前的方法，例如微球和各种冲洗 技术，是非连续的并且仅限于稳态流动 状况。 其中最好的只能产生眼部血液的“快照” 在某一时间点流动。 我们将利用激光多普勒流量计 测量来自眼睛表面角膜缘（前部）的血流量 段）和赤道处（脉络膜血流）。 新开发的敏感 时差超声波流量计将用于直接测量血液 从向眼睛前部供血的两条动脉之一流出 （长睫状后动脉）。 这两种方法都提供了 连续的高频响应。 激光多普勒血流计具有较高的 度空间分辨率，而超声波流量计会产生更多 全球测量流程。 使用这些技术，确定改变的效果 局部血流的灌注压力将通过实验确定 增加或减少眼内压和全身血液 压力。 区域自治的程度和作用 交感神经输入将被确定。 肾上腺素能药物（均 兴奋剂和阻滞剂）将用于系统地定义存在 肾上腺素能受体亚型在这些区域中的作用及其相对作用 血管床。 近年来，越来越明显的是，颠覆 眼睛正常循环功能的障碍可能会直接导致或加剧 青光眼等多种病症的病理生理学 视网膜病变和黄斑变性。 此外，大部分药物 目前用于或拟用于治疗青光眼的有 对眼部血管有明显作用。 希望信息 从这个研究项目中获得的成果将增强我们对眼部的了解 一般生理学和药理学。 更具体地说，这些结果 应该扩大我们对这些特定肾上腺素能亚型的了解 血管床，应该有助于设计新的治疗方法 具有更高受体特异性和更少不良副作用的药物。