PERIPHERAL MICROVASCULAR CONTROL MECHANISMS

外周微血管控制机制

• 批准号: 2080972
• 负责人: LOUIS A KOMAN
• 金额: $ 13.46万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-15 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2080972
• 关键词: Raynaud's disease; adrenergic receptor; cardiovascular pharmacology; cell type; cold temperature; disease /disorder model; hemodynamics; ischemia; laboratory rabbit; limbs; microcirculation; narcotic antagonists; norepinephrine; peripheral nervous system; phenylephrine; prazosin; stimulant /agonist; sympathectomy; thermoreception; vasoconstriction; vasodilation

Altered activities of daily living and decreased work productivity secondary to pain on exposure to old, "cold intolerance," are a significant societal burden. A better understanding of the mechanisms of microvascular regulation will provide insight into cold intolerance and aid clinical management. The altered digital microvascular blood flow and cold intolerance seen after trauma or with vascular compromise occlusive, vasospastic, or vaso-occlusive disease) affects millions of people. The cold intolerance of Raynaud's disease and scleroderma preferentially affects woman of childbearing age; black women are affected more often than white women. Surgical peripheral sympathectomy, which appears to improve blood flow by interrupting sympathetic vasoconstrictor innervation, is used when less invasive treatment fails. Paradoxically, digital amputation results in complete sympathectomy and cold intolerance of the replanted digit. The mechanism(s) causing post-replantation vascular thermoregulatory abnormalities is not known, but supersensitivity of digital adrenergic receptors may be a partial explanation. This study hypothesizes that the digital microvascular responses to cold stress following complete sympathectomy differ functionally from those following peripheral sympathectomy. Specifically, the initial vasodilation following complete sympathectomy is replaced by vasoconstriction which results from an increased sensitivity of adrenergic receptors to agonist neurotransmitters. In contrast, this marked supersensitivity of adrenergic receptors does not follow peripheral sympathectomy. To test this hypothesis, a rabbit ear model has been developed in which chronic arterial pressure, auricular blood flow conductance, microvascular perfusion, and microvascular diameters can be monitored in awake, unanesthetized animals pre- and post-sympathectomy and while receptor agonist/antagonists are being manipulated. An acute rabbit ear preparation has also been developed to characterize adrenergic receptor subtypes participating in peripheral microvascular control by direct observation of the microcirculation during application of alpha-1 and alpha-2 agonists and antagonists. Five separate protocols will establish: l) the adrenergic receptor subtypes responsible for control of auricular blood flow, 2) the effect of sympathectomy on auricular conductance and microvascular dimensions, 3) the post-sympathectomy functional changes in receptor sensitivity, and 4) the identification of the receptor subtype having the maximal influence on functional supersensitivity. Together, these experiments will characterize the relationship between the adrenergic system and sympathectomy-related, cold-evoked vascular responses.

日常生活活动改变，工作效率下降 继发于疼痛的老接触，“冷不耐受”，是一个 沉重的社会负担。更好地理解 微血管调节将提供对寒冷不耐受的深入了解， 辅助临床管理。 手指微血管血流的改变， 外伤后或血管闭塞性损伤后出现耐寒， 血管痉挛或血管闭塞性疾病）影响数百万人。 的 以雷诺氏病和硬皮病的不耐寒为主 影响育龄妇女;黑人妇女更经常受到影响 而不是白色女人。 外科外周交感神经切除术，似乎 通过阻断交感血管收缩剂改善血流 当微创治疗失败时使用。 巧合的是， 手指截肢导致完全交感神经切除术和冷耐受 移植的手指导致再植后的机制 血管温度调节异常尚不清楚，但超敏感性 数字肾上腺素能受体可能是一个部分解释。本研究 假设手指微血管对冷应激的反应 完全交感神经切除术后的功能不同于 外周交感神经切除术 具体来说，最初的血管舒张 在完全交感神经切除术后， 肾上腺素能受体对激动剂的敏感性增加 神经传递素 相反，这标志着对 肾上腺素能受体不跟随外周交感神经切除术。 测试 根据这一假设，已经开发了一种兔耳模型， 动脉压，耳廓血流传导，微血管 灌注和微血管直径可以在清醒时监测， 交感神经切除术前后和while受体的未麻醉动物 激动剂/拮抗剂被操纵。 急性兔耳 还开发了一种用于表征肾上腺素能受体的制剂 直接参与外周微血管控制的亚型 在应用α-1期间观察微循环， α-2激动剂和拮抗剂。 五个独立的协议将建立： l）负责控制耳的肾上腺素能受体亚型 2）交感神经切断对心房传导的影响， 交感神经切除术后的功能变化， 受体敏感性，以及4）受体亚型的鉴定 对功能性超敏反应的影响最大。 我们一起努力， 这些实验将描述 肾上腺素能系统和交感神经切除术相关的冷诱发血管 应答