OXYTOCINERGIC EFFECTS ON CEREBRAL HEMODYNAMICS

催产素对脑血流动力学的影响

• 批准号: 2226835
• 负责人: DAVID W BUSIJA
• 金额: $ 20.61万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226835
• 关键词: cerebral hemorrhage; cerebral ischemia /hypoxia; cerebrospinal fluid; eicosanoid metabolism; glia; hormone regulation /control mechanism; immunocytochemistry; immunologic assay /test; newborn animals; oxytocin; prostaglandins; radioimmunoassay; respiratory distress syndrome of newborn; swine; tissue /cell culture; vascular endothelium; vascular resistance; vascular smooth muscle

Our overall hypothesis is that oxytocin is an important contributor to neonatal cerebrovascular control especially following pharmacological and pathological impairment of the prostaglandin synthetic system. Our hypothesis is supported by several interconnecting findings in newborn pigs: 1) Oxytocin levels increase in cerebrospinal fluid (CSF) and plasma to vasoactive levels during stressful conditions such as asphyxia, increased intracranial pressure, and osmotic stress; 2) Indomethacin pretreatment reverses cerebral arteriolar responses to oxytocin from dilation to potent constriction; 3) Indomethacin pretreatment alters oxytocinergic vascular responses in both pial arterioles and basilar artery; and 4) Pathological conditions such as global ischemia and the presence of subarachnoid blood cause impairment of prostaglandin-dependent responses in the cerebral circulation. Based upon our findings and those in the literature, we propose the following specific hypotheses: 1. Cerebral resistance vessels are exposed to vasoactive levels of oxytocin via CSF and plasma; 2. Prostaglandin synthetic capabilities of cerebral tissues and/or vessels are an important determinant of cerebrovascular responses to oxytocin; and 3. Impairment of the prostaglandin system by pathological stimuli results in altered responsiveness of cerebral arteries and arterioles to oxytocin. To test these hypotheses, three specific aims will be addressed using newborn pigs: 1. CHARACTERIZATION OF OXYTOCINERGIC EFFECTS ON CEREBROVASCULAR HEMODYNAMICS; 2. INVESTIGATION OF THE CONTRIBUTION OF PROSTAGLANDINS TO CEREBROVASCULAR RESPONSES TO OXYTOCIN; and 3. DETERMINATION OF CEREBROVASCULAR EFFECTS OF OXYTOCIN FOLLOWING PATHOLOGICAL ALTERATIONS IN THE PROSTAGLANDIN SYSTEM. We will use several complimentary methods for studying cerebrovascular responses, including the closed cranial window and intravital microscopy for characterization of individual arteries and arterioles in vivo, radioactive microspheres for determination of total and regional cerebral blood flow, microvascular measurement of blood pressure for determination of segmental resistance, and in vitro approaches for examining vascular responses in isolation. In addition, we will determine oxytocin and prostaglandin levels by radioimmunoassay. This investigation will explore control mechanisms in neonatal animals during normal and pathological conditions. We hope that our findings will be of clinical relevance and lead to therapies that improve outcome in stressed babies.

我们的总体假设是催产素是造成的重要因素 新生儿脑血管控制，特别是在药理和 前列腺素合成系统的病理障碍。我们的 新生儿中的几个相互联系的发现支持了假设 猪：1）催产素水平增加脑脊液（CSF）和血浆 在压力状况（例如窒息）中达到血管活性水平， 颅内压增加和渗透应激； 2）吲哚美辛 预处理逆转大脑小动脉对催产素的反应 扩张到有效的收缩； 3）放氨基霉素预处理改变 催产动脉和基底的催产毒素能血管反应 动脉; 4）等病理状况，例如全球性缺血和 蛛网膜下腔血液的存在导致前列腺素依赖性障碍 大脑循环中的反应。根据我们的发现和那些 在文献中，我们提出以下特定假设：1。 脑电阻容器暴露于血管活性水平的催产素水平 通过CSF和血浆； 2。脑的前列腺素合成能力 组织和/或血管是脑血管的重要决定因素 对催产素的反应；和3。损害前列腺素系统 病理刺激导致脑反应改变 动脉和动脉到催产素。为了检验这些假设，三个 具体目标将使用新生猪解决：1。表征 催产对脑血管血流动力学的影响； 2。调查 前列腺素对脑血管反应的贡献 催产素;和3。测定催产素的脑血管作用 遵循前列腺素系统的病理改变。 我们将 使用几种免费方法来研究脑血管反应， 包括闭合的颅窗和插入式显微镜 体内的单个动脉和动脉的表征， 放射性微球，用于测定总脑和区域大脑 血流，血压的微血管测量以确定 分段抗性和用于检查血管的体外方法 孤立的响应。 此外，我们将确定催产素和 Prostaglandin水平通过放射免疫测定法。这项调查将探索 正常和病理期间新生动物的控制机制 状况。我们希望我们的发现将具有临床相关性，并且 导致疗法改善压力婴儿的预后。