Temporal effects of inflammation on the autonomic control of circulation during exercise in type 2 diabetic rats

项目总结/摘要 由后肢骨骼肌收缩引起的反射是一种重要的神经机制， 负责心血管对运动的调节。这些调整，其中包括增加 外周血管阻力、心脏收缩力和心率，用于增加动脉血流量， 氧气运动的肌肉，并反过来支持他们的能力，以合同。这种神经机制已经被 称为运动加压反射，其传入臂由III和IV组传入纤维组成， 位于肌筋膜内和附近。第三组和第四组传入神经通常受到糖尿病的影响 这通常导致周围神经病变，引起从异常性疼痛到痛觉过敏， 痛觉减退。慢性炎症是外周炎症的已知机制之一， 神经病变，直接影响III组和IV组传入神经，存在于糖尿病、衰老和心血管疾病中 疾病实验的总体目标是阐明促炎细胞因子的作用 对运动加压反射的影响在拟议的实验中，我们将特别注意 注意已知在糖尿病患者和患有糖尿病的患者中上调的两种重要的促炎细胞因子， 心血管疾病，即白细胞介素1 β（IL-1β）和白细胞介素6（IL-6）。我们还将特别支付 注意两种重要的抗炎细胞因子，已知在糖尿病患者和患有糖尿病的患者中下调， 心血管疾病，即白细胞介素10（IL-10）和白细胞介素4（IL-4）。我们将在去大脑， 非麻醉大鼠的升压，心脏加速器，和交感神经活动的反应，静态和间歇性 在细胞因子受体的药理学阻断之前和期间的收缩。拟议 实验还将使用定量这些循环细胞因子的潜在上调或下调 多重测定中的血清样品。我们预计，这些实验将提供新的信息， 促炎细胞因子和抗炎细胞因子在糖尿病进展中对循环自主控制的作用 在运动中。

PROJECT SUMMARY/ABSTRACT A reflex arising from the contraction of hindlimb skeletal muscles is an important neural mechanism that is responsible for the cardiovascular adjustments to exercise. These adjustments, which include increases in peripheral vascular resistance, cardiac contractility and heart rate, function to increase arterial blood flow and oxygen to the exercising muscles, and in turn support their ability to contract. This neural mechanism has been named the exercise pressor reflex, and its afferent arm is comprised of group III and IV afferents whose endings are located in and near the muscle interstitium. Group III and IV afferents are commonly affected by diabetes which often results in peripheral neuropathy causing a range of problems from allodynia to hyperalgesia to hypoalgesia as the disease progresses. Chronic inflammation is one of the known mechanisms for peripheral neuropathy, directly affecting group III and IV afferents, and is present in diabetes, aging, and cardiovascular disease. The overall goal of the experiments proposed is to shed light on the role of pro-inflammatory cytokines on the exercise pressor reflex as diabetes progresses. In the proposed experiments, we will pay particular attention to two important pro-inflammatory cytokines known to be upregulated in diabetics and those with cardiovascular disease, namely interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). We will also pay particular attention to two important anti-inflammatory cytokines known to be downregulated in diabetics and those with cardiovascular disease, namely interleukin 10 (IL-10), and interleukin 4 (IL-4).We will examine in decerebrated, unanesthetized rats the pressor, cardioaccelerator, and sympathetic activity responses to static and intermittent contraction both before and during pharmacological blockade of the cytokine receptors. The proposed experiments will also quantify the potential up-regulation or down-regulation of these circulating cytokines using serum samples in multiplex assays. We anticipate that these experiments will provide new information about the role of pro- and anti-inflammatory cytokines in the progression of diabetes on the autonomic control of circulation during exercise.