Neural and non-neural modulators of skin blood flow and sweating in humans

人类皮肤血流和出汗的神经和非神经调节剂

• 批准号: 7273656
• 负责人: CRAIG G CRANDALL
• 金额: $ 32.26万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7273656
• 关键词: Acclimatization; Acetylcholine; Address; Adrenergic Agents; Aerobic Exercise; Affect; Aging; Antihypertensive Agents; Attenuated; Benchmarking; Binding; Blood Circulation; Blood Plasma Volume; Blood Pressure; Blood Vessels; Blood flow; Cardiac Output; Cholinergic Agents; Condition; Congestive Heart Failure; Coupled; Cutaneous; Data; Diabetes Mellitus; Disease; Doctor of Philosophy; Elevation; Event; Exercise; Exposure to; Heart failure; Heat Stress Disorders; Heating; Hour; Human; Incidence; Individual; Intercellular Fluid; Laboratories; Maintenance; Microdialysis; Multiple Sclerosis; Muscarinic Acetylcholine Receptor; Nerve; Nitric Oxide; Norepinephrine; Numbers; Outcome; Peptides; Physiologic Thermoregulation; Production; Rate; Reflex action; Regulation; Relative (related person); Reporting; Research Personnel; Sampling; Secondary to; Skin; Skin Temperature; Sweat; Sweat Glands; Sweating; Symptoms; Synapses; Syncope; System; Techniques; Temperature; Testing; Tissues; Training; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; blood pressure regulation; cholinergic; experience; heat stimulus; improved; innovation; insight; neuromechanism; neuroregulation; programs; relating to nervous system; response; vascular bed

DESCRIPTION (provided by applicant): A large fraction of cardiac output (i.e. greater than 50%) can be distributed to skin during heat stress, thus control of skin blood flow is vital for blood pressure regulation during a hypotensive challenge. Neural control of the cutaneous vasculature is unique relative to many vascular beds in that it is governed by both a sympathetic vasoconstrictor system and a separate sympathetic cholinergic active vasodilator system. Adding to this complexity, direct local heating of the skin induces cutaneous vasodilation via an entirely different mechanism (i.e. non-neural and primarily nitric oxide dependent). Moreover, profuse sweating that occurs during heat stress contributes to impaired blood pressure control if plasma volume is sufficiently reduced. Sweating occurs through the engagement of a sympathetic cholinergic system that may or may not be related to the cutaneous active vasodilator system. Classically, these systems (i.e. vasoconstrictor, vasodilator, and sweating systems) have been viewed as being independent, without one system affecting the other. However, preliminary data suggest significant interaction between these systems. In heat stressed individuals the degree of interaction and the importance of this interaction with respect to blood pressure and temperature regulation remain unclear. To this end, the projects outlined in this application will address the following three specific aims: 1) Test the hypothesis that substances released from the cutaneous active vasodilator nerve attenuate cutaneous vasoconstrictor responses through pre- and post- synaptic mechanisms; 2) Test the hypothesis that local heating attenuates cutaneous vasoconstrictor responsiveness through nitric oxide dependent and independent mechanisms; 3) Test the hypothesis that sweat glands are sensitized by mechanisms associated with local heating and through engagement of the cutaneous active vasodilator system. These objectives will be accomplished by combining the innovative technique of intradermal microdialysis to locally deliver pharmacological agents and regionally sample interstitial fluid, with the simultaneous assessment of skin blood flow and sweat rate. Findings from these studies will provide new insight into neural control of skin blood flow and sweating and how these responses can be affected by non-neural events. This information will prove valuable on two fronts: 1) it will identify mechanisms contributing to an increased incidence of fainting in heat stressed individuals, and 2) it will provide a valuable benchmark from which subsequent studies can be performed to better understand how neural and non-neural modulators of skin blood flow and sweating may be altered by disease (i.e. diabetes, heart failure, etc) and non-disease (i.e. aging) conditions.

描述（由申请人提供）：在热应激期间，大量心脏输出（即大于50％）可以分布给皮肤，因此，在降压挑战期间，控制皮肤血流对于血压调节至关重要。皮肤脉管系统的神经控制相对于许多血管床是独特的，因为它既受同情血管收缩系统和单独的交感神经能活性血管扩张剂系统的控制。除了这种复杂性外，皮肤的直接局部加热通过完全不同的机制（即非神经和主要依赖一氧化氮）引起皮肤血管舒张。此外，如果血压体积充分降低，则在热应激期间发生的大量出汗会导致血压控制受损。出汗是通过可能与皮肤活性血管舒张系统无关的交感神经胆碱能系统的参与而发生的。从经典上讲，这些系统（即血管收缩，血管扩张器和出汗系统）被视为独立，而没有一个系统影响另一个系统。但是，初步数据表明这些系统之间的显着相互作用。在热应力的个体中，这种相互作用的程度和这种相互作用在血压和温度调节方面的重要性尚不清楚。为此，本申请中概述的项目将解决以下三个具体目的：1）检验以下假设：从皮肤活性血管舒张神经释放的物质通过突触前和突触后机制释放出皮肤血管收缩剂反应； 2）检验以下假设：局部加热通过一氧化氮依赖和独立机制减弱皮肤血管收缩反应性； 3）检验以下假设：汗腺与局部加热相关的机制以及通过皮肤活性血管舒张系统的参与来敏感。这些目标将通过将皮内微透析的创新技术结合到局部提供药理药物和区域样品间质流体，并同时评估皮肤血液流量和汗液速率，从而实现这些目标。这些研究的发现将为皮肤血流和出汗的神经控制以及这些反应如何受到非神经事件的影响。该信息将在两个方面证明是有价值的：1）它将确定有助于增加热压力的个体晕厥发生率的机制，2）它将提供一个有价值的基准，可以从该基准中进行随后的研究，以更好地了解神经和非神经血液流动和汗水的神经和非神经调节剂如何因疾病而改变（即糖尿病（即心脏失败）（即心脏失败等），以及DIS的疾病（即）。