VASCULAR METABOLISM AND ITS RELATION TO FUNCTION

血管平滑肌对循环调节的张力维持 肌肉（VSM）与代谢密切相关。 基质知识 利用点和控制点，这两个知之甚少的方面， 了解血管代谢，将解决这个项目。 虽然VSM 主要是一种氧化组织，底物还没有明确地 鉴定 氧化组织的性质，底物还没有被 明确识别。 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， 呼吸商（RQ）。 假设底物利用率是 将通过测量RQ作为一个函数， 基质、刺激模式和收缩性。 利用总体 根据RQ研究设定的方向，将使用底物放射性同位素来完全 指定使用模式。 第二个主要的差距是， 血管代谢与观察结果有关， 在这种条件下，进入VSM的大部分葡萄糖仅被分解代谢为乳酸。 这种有氧糖酵解经常被认为是血管紧张素Ⅱ的一个指标。 肌病;然而，最近的证据从我的实验室表明，它是 与正常VSM中的Na-K转运有关。 有氧运动的控制点 糖酵解将确定和假设，钠钾运输是 将测试与糖酵解特异性偶联的化合物。 这将包括 测定，在糖酵解通过改变Na-K 运输，葡萄糖转运作为限速步骤的作用，并从 糖酵解中间体的测量，限速酶促步骤。 到 指定碳水化合物催化剂，糖原分解的作用将通过以下方式评估： 直接测量糖原分解和通过测量 糖原磷酸化酶的活化。 来自肺部和全身的血管 将研究流通与长期目标有关的具体 正常血管功能的底物利用模式， 除了收缩性之外，还可以使用更敏感的代谢变化， 检测和表征血管性肌病。

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.