VASCULAR METABOLISM AND ITS RELATION TO FUNCTION

血管顺畅维持循环调节的张力 肌肉(VSM)与新陈代谢密切相关。关于衬底的知识 使用点和控制点，这两个鲜为人知的方面是 了解血管新陈代谢，将通过这个项目来解决。而VSM 主要是氧化组织，底物并不明确 已确认身份。氧化组织的性质，底物还没有被 毫不含糊地确定。氧化底物的性质将是 使用O2消耗和CO2产生的测量进行评估，以建立 呼吸商(RQ)。底物利用率是 依赖于代谢需求将通过测量RQ作为函数进行测试 底物、刺激方式和收缩能力。利用总体上的 由RQ研究确定的方向，底物放射性同位素将被完全用于 指定使用模式。我们在理解上的第二个主要差距 血管新陈代谢与观察到的在全氧状态下 在此条件下，进入VSM的大部分葡萄糖只分解为乳酸。 这种有氧糖酵解经常被认为是血管的一种指标。 肌病；然而，最近来自我的实验室的证据表明 与正常VSM的Na-K转运有关。有氧运动的控制点 糖酵解将被确定，并假设Na-K转运是 具体结合糖酵解将进行测试。这将包括 在糖酵解因Na-K变化而改变的条件下的测定 转运，葡萄糖转运作为限速步骤的作用，以及从 糖酵解中间体的测量，这是限速酶步骤。至 具体说明碳水化合物分解代谢，糖原分解的作用将通过 糖原分解的直接测量及其控制 糖原磷酸化酶的激活。来自肺和全身的血管 将研究分发情况，长期目标是将具体的 底物利用模式到正常的血管功能，从而潜在地 除了收缩功能外，还可以使用更敏感的代谢变化来 检测并确定血管肌病的特征。

The maintenance of tone underlying circulatory regulation by vascular smooth muscle (VSM) is closly coupled to metabolism. Knowledge of the substrates utilized and control points, two poorly understood aspects central to understanding vascular metabolism, will be addressed by this project. While VSM is primarily an oxidative tissue, the substrate has not been unambiguously identified. The nature of the oxidative tissue, the substrate has not been unambiguously identified. The nature of the oxidative substrate will be assessed using measurement of O2 consumption and CO2 production to establish the respiratory quotient (RQ). The hypothesis that substrate utilization is dependent on metabolic demand will be tested by measuring the RQ as a function of substrate, mode of stimulation and contractility. Utilizing the overall direction set by RQ studies, substrate radioisotopes will be used to completely specify utilization patterns. A second major gap in our understanding of vascular metabolism relates to the observation that under fully oxygenated conditions, most of the glucose entering VSM is catabolized only to lactate. This aerobic glycolysis has often been proposed as an index of vascular myopathy; however, recent evidence from my laboratory indicats that it is related to Na-K transport in normal VSM. The control points for aerobic glycolysis will be determined and the hypothesis that Na-K transport is specifically coupled to glycolysis will be tested. This will include determination, under conditions in which glycolysis is altered by varying Na-K transport, of the role of glucose transport as a rate-limiting step, and from measurements of glycolytic intermediates, the rate-limiting enzymatic steps. To specify carbohydrate catabolism, the role of glycogenolysis will be assessed by direct measurement of glycogen breakdown and its control by measurement of the activation of glycogen phosphorylase. Vessels from both pulmonary and systemic circulations will be studied with the long-term goal of relating specific substrate utilization patterns to normal vascular function so that potentially more sensitive metabolic changes can be used in addition to contractility to detect and characterize vascular myopathy.