LOCAL REGULATION OF MICROVASCULAR FUNCTION

微血管功能的局部调节

• 批准号: 3334526
• 负责人: BRIAN R DULING
• 金额: $ 12.9万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3334526
• 关键词: adenosine; arachidonate; arterioles; body fluid osmolarity; cell type; cytochrome P450; diabetic angiopathy; erythrocytes; fatty acid metabolism; hamsters; hypertension; microcirculation; oxygen transport; peripheral blood vessel; reactive hyperemia; sickle cell crisis; striated muscles; vascular resistance

Vascular function is integrated with the needs of the organism by neural and humoral control processes. Control processes intrinsic to the tissue allow the functional demands of individual organs to be accommodated with minimal disturbances to the organism as a whole. These local control systems modulate blood flow into the tissue, distribution of flow within the tissue, and diffusion distances. There is substantial evidence that altered function of the regulatory process leads to such diverse pathological changes as hypertension and sickle cell crisis, and diabetic angiopathy. Oxygen plays a pivotal role in the regulatory process, either as a substrate whose delivery or concentration is regulated, or as a key substrate in metabolism. We have recently developed new techniques which permit us to carry out studies of the local control process at the level of the microcirculation. We can measure convective transport of oxygen in vessels as small as 15 microns in diameter, and we can study the reactivity of arterioles in vitro to a variety of substances including oxygen. In the research program proposed in this grant application, we will use these techniques to study the role of oxygen in the regulatory process in skeletal muscle microcirculation. We will: (1) quantitate red cell and oxygen delivery and the distribution of these through the microcirculation; (2) examine the relative contributions of alterations in oxygen delivery and oxygen distribution ot the regulatory process; (3) investigate the relative contributions of small arteries, large arterioles, small arterioles, and capillaries to flow regulation and to modulation of diffusion distance; (4) ascertain the cell type responsible for the oxygen sensitivity of arterioles; and (5) test the hypothesis that cytochrome P450 and metabolites of arachidonic acid act as sensors mediating the action of oxygen. These experiments will be carried out on the cheek pouch as well as the cremaster, tibialis anterior, and gracilis muscles of the golden hamster.

血管功能与神经的需求相结合 和体液控制过程。 控制过程与组织固有 允许适应单个器官的功能需求 整个生物体的干扰最小。 这些本地控制 系统调节血液流入组织，流动分布 组织和扩散距离。 有大量证据表明 调节过程的功能改变导致如此多样化 病理变化是高血压和镰状细胞危机以及糖尿病的变化 血管病。 氧气在调节过程中起关键作用 作为调节交付或集中度或作为钥匙的底物 代谢中的底物。 我们最近开发了新技术 允许我们以 微循环。 我们可以测量氧气中的对流运输 直径小至15微米的血管，我们可以研究反​​应性 体外的小动脉与包括氧在内的多种物质。 在 在本赠款申请中提出的研究计划，我们将使用这些 研究氧气在调节过程中的作用的技术 骨骼肌微循环。 我们将：（1）定量红细胞和 氧气递送和通过微循环的分布； （2）检查氧变化的相对贡献 和氧气分布的调节过程； （3）调查 小动脉，大动脉，小的相对贡献 小动脉和毛细血管进行流动调节和调节 扩散距离； （4）确定负责氧气的细胞类型 小动物的敏感性； （5）检验细胞色素P450的假设 蛛网膜酸的代谢物作为传感器介导的作用 氧。 这些实验也将在脸颊袋上进行 作为克里米斯，胫骨前部和金色的肌肉肌肉 仓鼠。