CANDESARTAN EFFECT ON CARDIAC & SKELETAL MUSCLE RESPONSE TO INSULIN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 最近的证据表明，生理剂量的胰岛素输注可以诱导骨骼肌血管扩张，包括新血管的募集。由于微血管灌注的增加与营养物质和激素的组织输送增加有关，我们假设内源性血管紧张素II通过激活AT2R来增强人类骨骼肌和心肌中的微血管灌注，这一作用促进了胰岛素在肌肉中的输送和作用。在我们的方案中，我们将研究35名瘦削的健康成年人的骨骼肌和心脏的微血管灌注以及葡萄糖的利用。它们将分别在三种不同的条件下(随机分配)进行研究：1)单独使用坎地沙坦，2)单独使用胰岛素夹，3)使用坎地沙坦和胰岛素夹。之所以选择坎地沙坦，是因为它对AT1R产生了不可逾越的对抗。我们将使用多普勒超声和CEU(声学造影)测量血流和微血管灌注量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent evidence suggests that an insulin infusion at a physiologic dose induces skeletal muscle vasodilation, including the recruitment of new blood vessels. As increased microvascular perfusion is associated with increased tissue delivery of nutrients and hormones, we hypothesize that endogenous angiotensin II enhances microvascular perfusion in the skeletal and myocardial muscle in humans via the activation of AT2R and this action facilitates insulin delivery and action in muscles. In our protocol, we will study microvascular perfusion in skeletal muscle and heart as well as glucose utilization in 35 lean healthy adults. They will each be studied under three different conditions (randomly assigned) as follows: 1) Candesarten alone, 2) insulin clamp alone, 3) Candesarten and insulin clamp. Candesartan was chosen as it exerts an insurmountable antagonism against the AT1R. We will measure blood flow and microvascular perfusion using Doppler ultrasound and CEU (contrast-enhanced ultrasound).