SNS AND LUNG VASCULAR PERMEABILITY

SNS 和肺血管通透性

• 批准号: 3448562
• 负责人: MICHAEL B MARON
• 金额: $ 5.14万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3448562
• 关键词: animal poison; body fluids; disease /disorder model; dyes; electrostimulus; head /neck injury; intracranial pressure; lung; microcirculation; neuropharmacology; pulmonary circulation; pulmonary edema; sympathetic nervous system; trauma; vascular endothelium permeability; veratrum alkaloid

We will test the hypothesis that intense activation of the sympathetic nervous system (SNS) may cause an increase in pulmonary microvascular permeability to fluid and proteins. This question is of interest, because recent studies have suggested that an increased permeability might contribute to the development of neurogenic pulmonary edema, a form of edema which often occurs after central nervous system injury which evokes a massive centrally-mediated discharge of the SNS. Our basic approach will be to determine if the capability of the pulmonary microvasculature to sieve proteins relative to water during extravascular fluid filtration becomes impaired under these conditions. Alterations in this capability will be evaluated by analyzing changes in lymph flow and lymph protein concentration that may occur in an in situ canine lung preparation in which pure pre-nodal lung lymph will be collected. The normal capability of the microvasculature to sieve proteins will be evaluated in a control group of animals in which fluid filtration has been increased by raising left atrial pressure mechanically. Changes in lymph flow and lymph protein concentration occurring under these conditions will be compared with those observed in groups of animals in which the SNS has been stimulated either centrally or peripherally. Central stimulation will be evoked by intracranial drug administration (veratrine and tityustoxin) and by intracranial pressure elevation. Stellate ganglion and splanchnic nerve stimulation will be used to activate components of the SNS peripherally. The specific role of adrenergic receptors and the adrenal gland in mediating the changes in lung transvascular fluid and protein flux that occur in response to these stimuli will be further delinated by evaluating additional groups of animals following either Alpha-adrenergic blockade or adrenalectomy.

我们将检验交感神经的强烈激活 神经系统（SNS）可能导致肺微血管增加 对液体和蛋白质的渗透性。 这个问题很有趣，因为 最近的研究表明，增加渗透性可能 有助于神经源性肺水肿的发展， 中枢神经系统损伤后经常发生的水肿，会引发 大量中枢介导的SNS放电 我们的基本方法将 是为了确定肺微血管系统的能力， 在血管外液体过滤期间相对于水筛选蛋白质 在这种情况下会受到损害。 此功能的更改 将通过分析淋巴流量和淋巴蛋白的变化来评估 浓度可能发生在原位犬肺制备中，其中 将收集纯的结前肺淋巴液。 的正常能力， 将在对照组中评价筛选蛋白质的微血管系统。 通过抬高左心房增加液体滤过的动物 机械压力 淋巴流量和淋巴蛋白的变化 在这些条件下发生的浓度将与那些 在刺激SNS的动物组中观察到， 中心或外围。 中枢刺激会被 颅内给药（藜芦碱和tityustoxin）， 颅内压升高 星状神经节和内脏神经 刺激将被用于在外周激活SNS的组件。 肾上腺素能受体和肾上腺的特殊作用 介导肺经血管液体和蛋白质流量的变化， 对这些刺激的反应将通过评估进一步描述 在α-肾上腺素能阻滞或 肾上腺切除术