LOCAL REGULATION OF MICROVASCULAR FUNCTION

血管功能通过神经系统与机体的需要相结合， 和体液控制过程。 组织固有的控制过程 使各个器官的功能需求得到满足， 对整个生物体的干扰最小。 这些地方控制 系统调节进入组织的血流， 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了这种多样的 高血压、镰状细胞危象、糖尿病等病理改变 血管病 氧气在调节过程中起着关键作用， 作为其递送或浓度受到调节的底物，或作为关键 代谢底物。 我们最近开发了新技术， 使我们能够在以下层面上对当地的控制过程进行研究： 微循环 我们可以测量氧气的对流输送， 直径小至15微米的血管，我们可以研究 对包括氧气在内的各种物质的影响。 在 在这项资助申请中提出的研究计划，我们将使用这些 技术来研究氧在调节过程中的作用， 骨骼肌微循环 我们将：（1）定量红细胞， 氧气输送和这些通过微循环的分布; (2)检查氧气输送变化的相对贡献 和氧分布的调节过程;（3）调查 小动脉、大动脉、小动脉 微动脉和毛细血管的流动调节和调制 扩散距离;（4）确定负责氧的细胞类型 小动脉敏感性;（5）检验细胞色素P450 和花生四烯酸的代谢物作为传感器介导的作用， 氧气 这些实验也将在颊囊上进行 作为提睾肌，胫骨前肌和股薄肌的黄金 仓鼠。

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.