Regulation of sympathetic vasoconstriction in resting and contracting skeletal muscle

静息和收缩骨骼肌中交感血管收缩的调节

• 批准号: RGPIN-2020-04449
• 负责人: DeLorey, Darren
• 金额: $ 2.4万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=739238
• 关键词: Regulation; sympathetic; vasoconstriction; resting; contracting

The precise regulation of blood pressure and the distribution of blood flow are essential to ensure that vital organs and tissues receive an adequate supply of oxygen and other nutrients to sustain life. Blood pressure and tissue blood flow are controlled by carefully regulating resistance in arteries. Neural activity in the sympathetic nervous system leads to the release of chemical (neurotransmitters) that constrict peripheral blood vessels and increase arterial resistance. Therefore, the sympathetic nervous system is an important regulator of blood pressure, tissue blood flow and vascular function. The long-term objective of my research program is to establish a mechanistic understanding of sympathetic nervous system regulation of blood pressure and skeletal muscle blood flow at rest, during exercise and in response to physiological stress. I am also interested in understanding whether sympathetic nervous system control of the cardiovascular system can be enhanced. I aim to identify potential therapeutic targets and specific interventions that will produce adaptations and elucidate specific mechanisms responsible for the adaptations. My laboratory uses an integrative physiology experimental approach in combination with pharmacology and molecular techniques to investigate mechanisms that regulate sympathetic neurovascular control and plasticity from the cellular to the integrated systems level. The short-term objectives in this grant will investigate the role of pannexin-1 (Panx1) channels in a-adrenergic receptor mediated vasoconstriction and whether sex and exercise training modulate Panx1 function (Objective 1). Objectives 2-4 will investigate whether vanilloid-type transient receptor potential ion channels (Objective 2), cytochrome P450 enzymes (Objective 3) and adenosine triphosphate (Objective 4) alter sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle of sedentary and exercise trained males and females. Importantly, each objective includes a carefully designed exercise training intervention and sex-based analysis. This research will advance our understanding of the important physiological mechanisms involved in sympathetic nervous system control of the cardiovascular system. The research may also have important biomedical implications with respect to the control of blood pressure and the perfusion of vital organs and tissues at rest and in response to physiological stress (e.g. acute and chronic exercise). The proposed studies utilize an array of cutting edge experimental techniques and an integrative scientific approach which provides a rich training environment. I will continue to engage undergraduate and graduate students in my research, and thus, the research will contribute to the development of the next generation of scientific personnel and future research innovation and excellence in Canada.

血压的精确调节和血流的分布对于确保重要器官和组织获得足够的氧气和其他营养物质以维持生命至关重要。血压和组织血流量是通过仔细调节动脉阻力来控制的。交感神经系统中的神经活动导致化学物质（神经递质）的释放，从而收缩外周血管并增加动脉阻力。因此，交感神经系统是血压、组织血流量和血管功能的重要调节器。 我的研究计划的长期目标是建立一个机械的理解交感神经系统调节血压和骨骼肌血流在休息时，在运动和生理应激反应。我也有兴趣了解是否可以增强交感神经系统对心血管系统的控制。我的目标是确定潜在的治疗目标和具体的干预措施，将产生适应和阐明具体的机制负责的适应。我的实验室采用综合生理学实验方法，结合药理学和分子技术，研究从细胞到综合系统水平调节交感神经血管控制和可塑性的机制。本基金的短期目标是研究泛连接蛋白-1（Panx 1）通道在α-肾上腺素能受体介导的血管收缩中的作用，以及性别和运动训练是否调节Panx 1功能（目标1）。目的2-4将研究香草酸型瞬时受体电位离子通道（目的2）、细胞色素P450酶（目的3）和三磷酸腺苷（目的4）是否改变久坐和运动训练的男性和女性的静息和收缩骨骼肌的交感血管收缩反应性。重要的是，每个目标都包括精心设计的运动训练干预和基于性别的分析。这项研究将促进我们对交感神经系统控制心血管系统的重要生理机制的理解。这项研究还可能对血压控制以及重要器官和组织在休息时和对生理压力（如急性和慢性运动）的反应中的灌注具有重要的生物医学意义。 拟议的研究利用了一系列尖端的实验技术和综合科学方法，提供了丰富的培训环境。我将继续让本科生和研究生参与我的研究，因此，这项研究将有助于下一代科学人员的发展和加拿大未来的研究创新和卓越。