Unit Control of Muscle Blood Flow

肌肉血流的单位控制

• 批准号: 7217021
• 负责人: STEVEN S SEGAL
• 金额: $ 27.7万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7217021
• 关键词: arterioles; artery; biological signal transduction; blood pressure; cell cell interaction; electrophysiology; electrostimulus; exercise; hamsters; innervation; membrane channels; microcirculation; microelectrodes; motor neurons; muscle; muscle contraction; neuromuscular junction; neuropharmacology; sympathetic nervous system; tissue /cell preparation; vascular resistance; vascular smooth muscle nervous control; vasodilation; video microscopy

DESCRIPTION (provided by applicant): Our long term objectives are to provide new insight into the cellular signaling pathways that underlie the regulation of peripheral vascular resistance. The interaction between skeletal muscle contractions and sympathetic nerve activity (SNA) determines muscle blood flow and arterial pressure during exercise through governing the diameter of resistance vessels. The resistance network is comprised of arterioles embedded within the muscle and their feed arteries (FA) located extemal to the tissue. As motor unit recruitment and contractile activity increase, vasodilation is initiated on arterioles and "ascends" into FA via cell-to-cell conduction of a signal (hyperpolarization) along the endothelium that relaxes surrounding smooth muscle cells. Resistance vessels are invested with sympathetic nerves; thus, arterioles and FA constrict progressively as SNA increases. With SNA during exercise, dilation prevails in downstream arterioles while constriction prevails in upstream FA, which thereby restricts muscle blood flow. Our working hypothesis is that ascending (conducted) vasodilation is modulated by SNA to govem muscle blood flow while maintaining arterial pressure. Our Specific Aims are to: (1) Determine the signaling pathway(s) that initiate(s) ascending vasodUation; (2) Determine which ion channels underlie the initiation and the conduction of vasodUation; and (3) Determine how SNA modulates conducted vasodilation. Using the retractor muscle preparation in anesthetized hamsters, muscle fibers are stimulated to contract and vasomotor responses are observed using video microscopy. Individual FA are isolated and pressurized to record vasomotor and electrophysiological responses during conducted vasodilation and SNA. Underlying signaling pathways are investigated using specific pharmacological interventions, intracellular recording, and selective disruption of endothelium or smooth muscle function. Findings from these experiments will provide new, mechanistic insight into vascular determinants of physical performance and strengthen the foundation for understanding decrements in physical work capacity that occur with disease, inactivity, and aging. This insight will promote the development of novel strategies for the maintenance of an active lifestyle as well as rehabilitation and recovery from impaired physical work capacity.

描述（由申请人提供）：我们的长期目标是提供对作为外周血管阻力调节基础的细胞信号传导途径的新见解。 骨骼肌收缩和交感神经活动 (SNA) 之间的相互作用通过控制阻力血管的直径来决定运动过程中的肌肉血流量和动脉压。 阻力网络由嵌入肌肉内的小动脉及其位于组织外部的供给动脉 (FA) 组成。 随着运动单位募集和收缩活动的增加，小动脉开始血管舒张，并通过沿内皮细胞间的信号传导（超极化）“上升”至 FA，从而松弛周围的平滑肌细胞。 阻力血管布有交感神经；因此，随着 SNA 的增加，小动脉和 FA 逐渐收缩。 运动期间使用 SNA 时，下游小动脉会扩张，而上游 FA 会收缩，从而限制肌肉血流。 我们的工作假设是，SNA 调节上行（传导）血管舒张，以控制肌肉血流，同时维持动脉压。 我们的具体目标是： (1) 确定启动上行血管舒张的信号通路； (2)确定哪些离子通道是血管舒张的启动和传导的基础； (3) 确定 SNA 如何调节血管舒张。 在麻醉仓鼠中使用牵开器肌肉制剂，刺激肌纤维收缩，并使用视频显微镜观察血管舒缩反应。 单独的 FA 被隔离并加压，以记录进行血管舒张和 SNA 期间的血管舒缩和电生理反应。 使用特定的药理干预、细胞内记录和选择性破坏内皮或平滑肌功能来研究潜在的信号通路。 这些实验的结果将为了解身体机能的血管决定因素提供新的机制见解，并为理解疾病、不活动和衰老导致的体力工作能力下降奠定基础。 这一见解将促进新策略的开发，以维持积极的生活方式以及受损的体力工作能力的康复和恢复。