MECHANISMS OF CUTANEOUS ACTIVE VASODILATION

皮肤主动血管舒张机制

• 批准号: 6390872
• 负责人: DEAN L KELLOGG
• 金额: $ 21.35万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6390872
• 关键词: arm; body temperature regulation; bradykinin; cardiovascular pharmacology; clinical research; cyclic AMP; cyclic GMP; human subject; hyperthermia; microdialysis; nitric oxide; second messengers; skin circulation; ultrasound blood flow measurement; vasoactive intestinal peptide; vasodilation

DESCRIPTION (Adapted from the applicant's abstract):Almost 70 years ago the human cutaneous active vasodilator system was first described; however, its mechanisms remain unclear today. The long term goal of this project is to define the physiological mechanisms that effect cutaneous active vasodilation during thermoregulatory reflex responses to hyperthermia. This will contribute to our understanding of the role of the cutaneous circulation in adaptation to hot environments and understanding the increased morbidity and mortality of persons with limited cardiac output, including the aged and those with cardiac disease. An enhanced understanding of the cutaneous circulation may reduce mortality in the growing patient population that receives numerous pharmacological therapies that may predispose them to iatrogenic heat intolerance, heat stroke, and death. The following specific aims will be explored. 1) Determine whether bradykinin is involved in cutaneous active vasodilation during heat stress. 2) Clarify whether nitric oxide (NO) levels increase and cause cutaneous active vasodilation during heat stress or whether NO levels remain constant and functions as a permissive factor during heat stress. 3) Determine whether the nitric oxide required for cutaneous active vasodilation during heat stress is produced by endothelial nitric oxide synthase (eNOS) or by neuronal nitric oxide synthase (nNOS). 4) Determine the role of vasoactive intestinal polypeptide (VIP) in cutaneous active vasodilation during heat stress. 5) Determine the role of cAMP in cutaneous active vasodilation during heat stress. 6) Determine the role of cGMP in cutaneous active vasodilation during heat stress. Studies will be done in healthy humans. Intradermal microdialysis will be used to treat small areas of forearm skin with specific pharmacological agents to manipulate the bradykinin, nitric oxide, VIP, and second messenger systems. Laser-Doppler flowmetry will monitor skin blood flow responses during normothermia and hyperthermia at both drug-treated, experimental sites, and at adjacent untreated, control sites. In addition intradermal microdialysis will be combined with measurements of bioavailable NO by hemoglobin-trapping to define further how the NO system functions in cutaneous active vasodilation.

描述（改编自申请人的摘要）：大约 70 年前 首次描述人体皮肤主动血管扩张系统；然而，其 至今机制仍不清楚。该项目的长期目标是 定义影响皮肤主动血管舒张的生理机制 在对高热的体温调节反射反应期间。这将有助于 帮助我们了解皮肤循环在适应中的作用 炎热的环境并了解发病率和死亡率的增加 心输出量有限的人，包括老年人和心脏病患者 疾病。增强对皮肤循环的了解可能会减少 因接受大量治疗而不断增长的患者群体的死亡率 可能使他们易受医源性热影响的药物治疗 不耐受、中暑和死亡。将实现以下具体目标 探索过。 1) 确定缓激肽是否参与皮肤活性 热应激期间的血管舒张。 2) 澄清一氧化氮（NO）水平是否 在热应激期间增加并引起皮肤主动血管舒张或是否 NO 水平保持恒定，并在发情期间充当允许因素 压力。 3) 确定皮肤活性是否需要一氧化氮 热应激期间的血管舒张是由内皮一氧化氮产生的 合酶（eNOS）或神经元一氧化氮合酶（nNOS）。 4) 确定 血管活性肠肽（VIP）在皮肤活性中的作用 热应激期间的血管舒张。 5) 确定cAMP在皮肤中的作用 热应激期间主动血管舒张。 6) 确定cGMP的作用 热应激期间皮肤主动血管舒张。研究将在 健康的人类。皮内微透析将用于治疗小面积的 前臂皮肤上涂有特定的药物来操纵缓激肽， 一氧化氮、VIP 和第二信使系统。激光多普勒血流计将 监测正常体温和高温期间的皮肤血流反应 药物处理的实验点，以及邻近的未处理的对照点。在 此外，皮内微透析将与测量相结合 通过血红蛋白捕获生物可利用的一氧化氮，进一步定义一氧化氮系统如何 具有皮肤活性血管舒张功能。