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Sleep Disordered Breathing and Vasomotor Regulation

睡眠呼吸障碍和血管舒缩调节

基本信息

批准号：
7226301
负责人：
BARBARA J MORGAN
金额：
$ 34.49万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2009-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Sleep-disordered breathing has emerged as a risk factor for many forms of cardiovascular disease; however, the underlying mechanisms are incompletely understood. Our goal is to determine whether sleep-disordered breathing alters structure and function of resistance vessels in the cerebral and skeletal muscle circulations. We will investigate the time course and reversibility of these vascular alterations and examine the causative roles played by oxidant stress and sympathetic neural activation. Humans subjects with obstructive sleep apnea and rats exposed to chronic intermittent hypoxia (CIH) will be studied to address 4 specific aims. In Aim 1, we will perform in vitro studies of isolated, perfused middle cerebral and gracilis arteries of the rat to determine the time course and potential for reversibility of CIH-induced impairments in vascular structure and function. In addition, we will assess the roles of sleep fragmentation and cyclic dexoygenation/reoxygenation in causing CIH-induced alterations in vascular function. In Aim 2, we will use similar in vitro methods to determine whether oxidant stress contributes importantly to CIH-induced vascular dysfunction. In Aim 3, we use chemical and surgical sympathectomy and angiotensin II receptor blockade to assess the role of the sympathetic nervous system causing CIH-induced vascular dysfunction. In Aim 4, we will explore the functional consequences of CIH-induced vascular dysfunction in humans by assessing vasodilatory responses to acute episodes of hypoxia and hypercapnia before and after treatment of obstructive sleep apnea. The results of these experiments will further define the pathogenetic link between sleep-disordered breathing and cardiovascular disease and may lead to the development of a more rational approach to therapy for this common clinical condition.

描述（由申请人提供）：睡眠呼吸障碍已成为多种心血管疾病的危险因素;然而，其潜在机制尚未完全了解。我们的目标是确定睡眠呼吸障碍是否会改变大脑和骨骼肌循环中阻力血管的结构和功能。我们将研究这些血管改变的时间过程和可逆性，并研究氧化应激和交感神经激活所起的致病作用。将对患有阻塞性睡眠呼吸暂停的人类受试者和暴露于慢性间歇性缺氧（CIH）的大鼠进行研究，以解决4个特定目标。在目标1中，我们将进行离体研究，灌注大脑中动脉和股薄动脉的大鼠，以确定CIH诱导的血管结构和功能的损伤的可逆性的时间过程和潜力。此外，我们将评估睡眠片段化和周期性脱氧/复氧在引起CIH诱导的血管功能改变中的作用。在目标2中，我们将使用类似的体外方法来确定氧化应激是否对CIH诱导的血管功能障碍有重要作用。在目标3中，我们使用化学和外科交感神经切除术和血管紧张素II受体阻滞剂来评估交感神经系统引起CIH诱导的血管功能障碍的作用。在目标4中，我们将通过评估阻塞性睡眠呼吸暂停治疗前后对急性缺氧和高碳酸血症发作的血管舒张反应，探讨CIH诱导的人类血管功能障碍的功能后果。这些实验的结果将进一步确定睡眠呼吸障碍和心血管疾病之间的发病联系，并可能导致开发一种更合理的方法来治疗这种常见的临床疾病。