REGULATION OF CORONARY MICROVESSEL PERMEABILITY

无数的冠状动脉血管功能的变化，以适应运动训练的要求。在项目4中，重点是健康心脏的微血管交换如何适应运动训练的代谢需求。运动训练是否有改善高脂血症的效果。总体假设是，运动引起的冠状动脉交换能力的增加反映了微血管通透性（Ps）的功能变化。通过荧光显微荧光分光光度法在从正常饮食和高脂肪（HF）饮食的久坐（SED）和运动训练（EX）的猪的心脏分离的微血管中评估Ps。重要的发现是，运动训练后，小动脉对血管活性剂（如腺苷（ADO））的Ps反应在方向和幅度上发生变化。根据这些和其他重要的调查结果，拟议的工作有4个目标。目标1将侧重于交换屏障途径，目标2将侧重于白蛋白（游离脂肪酸的主要载体）与其他大分子相比穿越完整微血管壁的机制。ADO诱导EX猪小动脉Ps的NO依赖性增加和SED猪小动脉Ps的减少。由于ADO可以激活cAMP依赖性通路，NO可以激活cGMP依赖性通路，因此Aim 3将重点关注cAMP和cGMP在介导微血管Ps中的作用。在目的4中，我们将集中在ADO受体亚型介导的ADO诱导的变化，Ps在小动脉从SED和EX猪。项目4的数据说明了ADO在交换微血管水平上协调交换的新作用，增强了其在冠状动脉血流自动调节中的众所周知的作用。这项研究的结果影响了对运动和休息期间溶质输送的理解。知道训练影响溶质通量直接影响患者的训练状态不会改变药物输送或微血管对冠状动脉功能常见介质的反应的假设。

A myriad of coronary vascular functions change to accommodate the demands of exercise training. In PROJECT 4 the focus is on how microvascular exchange in healthy hearts adapts to match the metabolic demands exercise training. And whether exercise training ameliorates the effects of hyperlipidemia. The global hypothesis is that exercise-induced increases in coronary exchange capacity reflects functional changes in microvessel permeability (Ps). Ps is assessed by fluorescence microspectrofluoremetry in microvessels isolated from the hearts of pigs on a normal diet and ho a high fat (HF) diet that are sedentary (SED) and exercise trained (EX). The important finding is that following exercise training Ps responses of arterioles to vasoactive agents, such as adenosine (ADO), change in direction and magnitude. In light of these and other significant findings, the proposed work has 4 aims. Aim 1 will focus on exchange barrier pathways and Aim 2 will focus on the mechanisms by which albumin, the primary carrier of free fatty acids, in contrast to other macromolecules, traverses the walls of intact microvessels. ADO induced an NO-dependent increases in Ps in arterioles from EX pigs and a decrease in Ps of SED pig arterioles. As ADO can activate cAMP- dependent pathways and NO can activate cGMP-dependent pathways, Aim 3 will focus on the roles of cAMP and cGMP in mediating microvessel Ps. In Aim 4, we will focus on the ADO receptor subtypes which mediate ADO-induced changes in Ps in arterioles from SED and EX pigs. The data on PROJECT 4 illustrate a new role of ADO in the coordination of exchange at the level of exchange microvasculature augmenting its well known role in autoregulation of coronary blood flow. The results of this research impact both understanding solute delivery during bouts of exercise and during rest. Knowing that training influences solute flux impacts directly on the assumption that the training status of patients does not alter drug delivery or responses to the microvasculature to common mediators of coronary function.