CANDESARTAN EFFECT ON CARDIAC & SKELETAL MUSCLE RESPONSE TO INSULIN

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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).